with other antihypertensive drugs), or used in greater doses in acute and chronic renal
|
|
- Charlotte Dalton
- 5 years ago
- Views:
Transcription
1 3.1. Introduction Furosemide is a very efficient loop diuretic used in draining all kinds of edemas (of cardiac, hepatic or renal origin), in mild or moderate hypertension (itself or combined with other antihypertensive drugs), or used in greater doses in acute and chronic renal failure, in oliguria (Berkó et al. 2002). Erratic oral absorption (11 90%) is the main problem associated with the formulation and effectiveness of the Furosemide (FSM) (Jackson 2006; Akbuĝa et al. 1988; Chungi et al. 1979). According to Biopharmaceutical Classification System (BCS), FSM is classified as a class IV drug having low solubility and low permeability (Ozdmir and Ordu 1998; Boles Ponto and Schoenwald 1990). SNEDDS can be utilized to enhance drug solubilization in GIT and it has also an impact on permeability (Date et al. 2010; Porter et al. 2008; Tang et al. 2007). SNEDDS strategy has been experimented for furosemice (FSM), and various carriers have been tested (Zvonar et al., 2010). However, at present, no FSM marketed products arising from this approach are available, probably because of the unsatisfactory performance of the studied systems. The core objectives of the present study were to develop and evaluate an optimized self emulsifying drug delivery system for FSM and to assess its pharmacodynamic effect in terms of diuretic efficacy Material and methods Materials FSM was received as a gift sample from Torrent Pharmaceuticals Ltd., Ahmedabad, India. Maisine 35-1, Transcutol P and Lauroglycol 90 were generously provided by Gattefosse France. Cremophore RH 40 and Cremophore EL were received as gift sample from BASF, USA. Captex 355 EP/NF, Captex 300 EP/NF and Capmul MCM NF were a generous gift from Abitec Corporation, USA. Polyethylene glycol 400 (PEG Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 67
2 400) was purchased from Merck Limited, Mumbai, India. Oleic acid was purchased from S. D. Fine Chemicals Limited, Mumbai. Propylene glycol and Tween 80 were purchased from Thomas Baker Chemicals Limited, Mumbai. Castor oil USP was purchased from Arora Pharmaceuticals Private Limited, New Delhi. Empty hard gelatin capsules were obtained from Associated Capsules Pvt. Ltd, Mumbai. Dialysis Tubing (seamless cellulose tubing, MWCO 12000) was purchased from Sigma Chemical Co. USA. All other chemicals used were of analytical grade Preparations of solutions a. 0.1M sodium hydroxide solution: Solution of molarity 0.1M prepared by diluting 4 g of sodium hydroxide to 1000 ml with water. b. 0.1N hydrochloric acid solution: Solution of normality 0.1N prepared by diluting 8.5 ml of hydrochloric acid to 1000 ml with water. c. Phosphate buffer (ph 6.8): Dissolve g of disodium hydrogen orthophosphate and g of potassium dihydrogen orthophosphate in sufficient water to produce 1000 ml Identification of the drug The drug was identified by physical observations, melting point determination and Ultraviolet Spectroscopy (UV). a. Physical observations: The color and powder forms of drug were observed and identified as per IP 2007 specifications and compared significantly. b. Melting point: the melting point of furosemide sample was determined by melting point apparatus and compared with the melting point of reference sample as specified in the BP c. Ultraviolet Spectroscopy: A per cent w/v solution in 0.1 M sodium hydroxide was examined in the range of 220 nm to 360 nm. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 68
3 Calibration curve Standard calibration curve for furosemide was prepared by making solutions of different concentration in methanol as follows: 1, 2, 3, 4, 5 µg/ml and the absorbance was measured at 276 nm (UV-2202, Systronics, India). Standard calibration curve for furosemide was prepared by making solutions of different concentration in 1:1 ratio of methanol: phosphate buffer (ph 6.8) and ƛ max was determined (UV-2202, Systronics, India) Solubility studies These studies were performed to determine the solubility in individual vehicle. Highest solubility showing vehicles were then used for formulation of SNEDDS. Initially the solubility of FSM was determined in oils (i. e., Maisine 35-1, Capmul MCM, Captex 355 EP/NF, Captex 300 EP/NF, Oleic acid, Castor oil), surfactant (i. e. Tween 80, Lauroglycol 90, Cremophore RH 40 and Cremophore EL) and co-surfactants (Transcutol P, PEG 400, Propylene glycol). 2 ml of each vehicle was added in capped vial containing excess of FSM. These vials were stirred on a water bath maintained at 30 C for 48 hours. After attainment of equilibrium each vial was centrifuged at 5000 RPM for 10 min to separate the insoluble FSM and excess of insoluble FSM was removed by membrane filter of 0.22 µ pore size (Pall Life Sciences, India). Dissolved FSM was quantified by UV-spectrophotometer (UV-2202, Systronics, India) at 276 nm Pseudoternary phase diagram studies Water titration method was used for construction of phase diagram using oil and surfactant/co-surfactant mix (S mix ). Based on solubility studies, two sets of S mix (i.e., Tween 80: Transcutol P and PEG 400: Transcutol P) were investigated with Capmul MCM as the oil phase. Surfactant and co-surfactant were added in the ratio of 1:1, 2:1, 3:1 and 4:1 for both of the sets. Distilled water was added in a drop wise manner to the Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 69
4 mixture of certain weight ratios (i. e., 9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8, 1:9) of oil and surfactant/co-surfactant (S mix ). Then each mixture was observed for phase clarity and flowabilty. Phase diagrams were constructed by using trial version of CHEMIX School 3.50 software (Minnesota, USA) Preparation of SNEDDS formulations From the solubility study and ternary phase diagram studies, SNEDDS components were selected for FSM incorporation and a series of SNEDDS were prepared (Table 3.1) with varying ratio of oil to S mix. The series contained Capmul MCM (oil) and Tween 80/Transcutol P (S mix ). FSM (6.67 % w/w) was loaded into each mixture. Table 3.1: Composition of developed formulations for FSM. Formulation codes Capmul MCM Tween 80 Transcutol P Furosemide %w/w mg %w/w mg %w/w mg %w/w mg F F F F F F The FSM-SNEDDS was prepared by dissolving FSM into S mix in glass vials and accurately weighed oil was added. Components were mixed and heated (45 50 C) to form a homogenous mixture and stored at room temperature till further use Characterization and evaluation of formulations Dilution test SNEDDS formulation containing 40 mg of FSM (1 part) was diluted 10 times with distilled water, 0.1N HCl and phosphate buffer of ph 6.8 and observed. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 70
5 Drug content determination Pre weighted quantity of FSM containing SNEDDS were dissolved in 25 ml of methanol. FSM content was determined spectrophotometrically (UV-2202, Systronics, India) at 276 nm Emulsification time and precipitation assessment The emulsification time of SNEDDS formulation was assessed on USP II dissolution apparatus (Dolphin India). Each formulation (600 mg) was added drop wise to 500 ml of distilled water maintained at 37±0.5 C. Gentle agitation was provided by a standard stainless steel dissolution paddle rotating at 50 RPM. Precipitation was evaluated by visual assessment of the resultant emulsion after 24 h. The formulations were then categorized as clear (transparent or transparent with bluish tinge), non-clear (turbid), stable (no precipitation at the end of 24 h), or unstable (showing precipitation within 24 h) (Khoo et al. 1998) Percentage transmittance (ƛ max 560 nm) 1 ml of SNEDDS formulation was diluted 100 times with distilled water. Percentage transmittance were measured spectrophotometrically (UV-2202, Systronics, India) at 560 nm using distilled water as a blank Viscosity determination SNEDDS (1 ml) was diluted 10 times and 100 times with distilled water in a beaker with constant stirring on a magnetic stirrer. Viscosity of resulting nanoemulsion and initial SNEDDS were determined by using Brookfield R/S plus rheometer (Brookfield Engineering, Middleboro, MA). Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 71
6 Droplet size analysis and polydispersity index (PDI) determination SNEDDS formulation (600 mg) containing 40 mg of FSM was diluted to 100 ml and mixed gently by inverting the flask. The size of droplets hence formed and PDI was measured by using Zetasizer (Malvern Instruments) Zeta potential determination SNEDDS was diluted 10 times and 100 times with distilled water by constant stirring on a magnetic stirrer. Zeta potential of the resulting emulsion was determined by using Zetasizer (Malvern Instruments) In vitro dissolution studies In vitro dissolution studies were performed to evaluate the dissolution rate of SNEDDS. These studies were carried out in USP type II dissolution test apparatus (Dolphin, India) at 100 RPM in 900 ml of phosphate buffer (ph 6.8). The temperature was maintained at 37±0.5 C. SNEDDS formulations were filled in hard gelatin capsule (size 0) and used for dissolution studies; results were compared with plain FSM and marketed tablet of FSM (LASIX). Aliquots were withdrawn at 5, 10, 20, 30, 45 and 60 min intervals and filtered using 0.22 µ nylon membranes. The withdrawn samples were diluted suitably and analyzed for the FSM content UV spectrophotometrically at 276 nm against phosphate buffer (ph 6.8). An equal volume of the dissolution medium was replaced in the vessel after each withdrawal to maintain the sink condition. Each test was performed in triplicate (n=3), and calculated mean values of cumulative drug release were used while plotting the release curves In vitro diffusion studies Permeation of FSM through biological membrane was evaluated by in vitro diffusion studies carried out by using dialysis technique (Kadu et al. 2010; Paradkar et al. 2007). Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 72
7 One end of pretreated cellulose dialysis tubing (Tube was soaked for 3-4 hours in a solution of 2 % sodium bicarbonate and 1 mm EDTA. Then the tube was rinsed carefully with distilled water from inside as well outside) (7 cm in length) was tied with thread and 0.22 ml of SNEDDS formulation (equivalent to 15 mg FSM) was placed in it along with 0.78 ml of dialyzing medium (phosphate buffer ph 6.8). The other end of tubing was also tied with thread and was allowed to rotate freely in the dissolution vessel of a USP type II dissolution test apparatus that contained 900 ml dialyzing medium (phosphate buffer ph 6.8) maintained at 37 ± 0.5 C and stirred at 100 RPM. Aliquots were collected periodically and replaced with fresh dissolution medium and analyzed spectrophotometrically at 276 nm for FSM content In vivo pharmacodynamic studies In vivo study was approved and performed in accordance with the guideline of the animal ethics committee. All institutional and national guidelines for the care and use of laboratory animals were followed. The rats were housed individually in metabolic cages, controlled conditions of temperature (25 C) and a 12:12 h light/dark cycle. The study was conducted in four groups consisting of three male wistar rats weighing g. Animals were grouped as: Group I: Three rats for plain FSM drug suspension in 0.25% Carboxy Methyl Cellulose (FSM) Group II: Three rats for optimized SNEDDS formulation (F3) of FSM (SNEDDS) Group III: Three rats for 0.25% Carboxy Methyl Cellulose (Control) Group IV: Three rats for blank SNEDDS formulation (Placebo) The rats were fasted 15 hrs prior to the experiment. Suspension of FSM (15 mg/kg) and optimized SNEDDS formulation F3 (equivalent to 15 mg of FSM) was administered to animals by gavage performing doses. The four groups of rats were allocated to one of Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 73
8 four different treatments as summarized in Table 3.2. The groups were inverted after providing washout period of 72 hours to each group (Pires et al. 2011; Vogel 2002). Table 3.2: In vivo study design of pure FSM and FSM-SNEDDS. Treatment FSM SNEDDS Control Placebo Period 1 Group 1 Group 2 Group 3 Group 4 Washout period of 72 hours Period 2 Group 2 Group 3 Group 4 Group 1 Washout period of 72 hours Period 3 Group 3 Group 4 Group 1 Group 2 Washout period of 72 hours Period 4 Group 4 Group 1 Group 2 Group 3 Cumulative urine output was recorded at 60, 120, 180 and 240 minutes after oral administration of compounds. The urine volume was measured and a urine sample was taken for further analysis. Urinary sodium was determined in a flame photometer (F129, Systronics, India). Results were presented as mean ± S.E.M. (standard error of mean) and were analyzed by two-way analysis of variance followed by a Boferroni post hoc test. A p<0.05 was considered significant Stability studies Chemical and physical stability of the optimized FSM SNEDDS formulation was assessed at 40 ± 2 C/75 ± 5% RH as per ICH Guidelines. SNEDDS equivalent to 40 mg FSM was filled in size 0 hard gelatin capsules, packed in aluminum strips and stored for three months in stability chamber (CHM 10S, REMI Instruments Ltd, India). Samples were analyzed at 0, 30, 60 and 90 days for clarity, drug content and time required for 90% drug release (t 90% ). Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 74
9 3.3. Results & Discussion Identification of drug (a) Physical observation of drug reveals that furosemide is white, crystalline powder. (b) Melting point of furosemide was found to be C. (c) When examined in the range 220 nm to 360 nm, a per cent w/v solution in 0.1 M sodium hydroxide showed three absorption maxima at about 228 nm, 271 nm and 333 nm. The ratio of the absorbance at the maximum at about 271 nm to that at the maximum at about 228 nm is 0.52 to The above mentioned tests confirm the identity of the received drug furosemide Calibration curve Calibration curve of furosemide was prepared in methanol. ƛ max was found to be 276 nm (Figure 3.1). Figure 3.1: UV spectrophotometrical scanning of furosemide in methanol showing ƛ max at 276 nm. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 75
10 The concentration was increased in a predetermined way. Regression equation was calculated and utilized for quantitative estimation of drug in samples. The correlation coefficient found is given in Figure 3.3. Results are expressed as mean±sd (Table 3.3). Table 3.3: Absorbance vs concentration data for calibration curve. Concentration Absorbance (µg/ml) ± ± ± ± ± Absorbance y = 0.096x R² = Concentration (µg/ml) Figure 3.2: Calibration curve of furosemide in methanol Solubility Studies Solubility of drug substance is a key criterion for selection of components for developing a SNEDDS formulation. The self-emulsifying formulations consisting of oil, Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 76
11 surfactant, co-surfactant and drug should be a clear and monophasic liquid at ambient temperature. Solubility studies were performed to identify suitable oils, surfactants and co-surfactants that possess good solubilizing capacity for FSM (Table 3.4) (Results are expressed as mean±sd). As FSM was found to have maximum solubility in Capmul MCM, Tween 80, Transcutol P and PEG 400, further studies were conducted using various combinations of these oils and surfactants to identify the self emulsifying area. Two sets of S mix and oil in different ratios were used to construct ternary phase diagrams. They were (1) Tween 80 and PEG 400 as S mix and Capmul MCM as oil phase and (2) Tween 80 and Transcutol P as S mix and Capmul MCM as oil phase. For both the sets the selected ratios of S mix were 1:1, 2:1, 3:1 and 4:1. Table 3.4: Solubility studies of FSM in various vehicles. Vehicle Function in SNEDDS Solubility (mg/ml) Maisine 35-1 Oil 3.16±0.84 Oleic Acid Oil 1.81±0.49 Capmul MCM Oil 6.14±0.46 Castor oil Oil 2.19±0.68 Captex 355 EP/NF Oil 0.24±0.07 Tween 80 Surfactant 91.12±2.86 Cremophore EL Surfactant 49.10±1.73 Cremophore RH 40 Surfactant 27.11±1.06 Span 20 Surfactant 22.16±0.63 Lauroglycol 90 Surfactant 1.70±0.82 PEG 400 Co-surfactant ±2.52 Propylene Glycol Co-surfactant 20.78±0.94 Transcutol P Co-surfactant ±2.45 Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 77
12 Pseudoternary phase diagram studies Self-nanoemulsifying systems form fine oil water emulsions with gentle agitation, upon their introduction into aqueous media. Surfactant gets preferentially adsorbed at the interface, reducing the interfacial energy as well as providing a mechanical barrier to coalescence. The Figure 3.4A, B, C and D and Figure 3.5A, B, C and D show ternary phase diagrams of Tween 80-PEG 400 (S mix ) and Capmul MCM as oil phase and Tween 80-Transcutol P (S mix ) and Capmul MCM as oil phase, respectively. The area in the shade indicates micro/nano emulsion region. Wider region indicates better selfemulsifying ability. The co-surfactant helps to achieve prerequisites of emulsion formation it helps in keeping the film flexible, fluid and tightly packed (Constantinides 1995). From the phase diagram studies it can be observed that as the S mix ratio increases the emulsion area decreases. Therefore the co-surfactant plays vital role in the emulsion formation for both of the S mix combinations. The phase study revealed that the emulsion region was more with Tween 80 Transcutol P (S mix ) in comparison to Tween 80-PEG 400 combination. Hence the Tween 80 Transcutol P (S mix ) was selected for FSM loading and further studies. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 78
13 Figure 3.3: Pseudo ternary phase diagrams with following components: Oil=Capmul MCM, Surfactant=Tween 80, Co-surfactant=PEG 400. S/Cos ratio of A is 1:1, B is 2:1, C is 3:1 and D is 4:1. S/Cos indicates Surfactant/Co-surfactant. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 79
14 Figure 3.4: Pseudo ternary phase diagrams with following components: Oil=Capmul MCM, Surfactant=Tween 80, Co-surfactant=Transcutol P. S/Cos ratio of A is 1:1, B is 2:1, C is 3:1 and D is 4:1. S/Cos indicates Surfactant/Cosurfactant Characterization and evaluation of formulations Dilution test The objective of dilution study was to study the degree of emulsification and recrystallization of the FSM, if any. Dilution may better mimic conditions in the stomach following oral administration of SNEDDS pre-concentrate. An accurate mixture of emulsifier is necessary to form a stable nano emulsion, for the development of SNEDDS formulation when one part of each SNEDDS formulation was diluted with Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 80
15 10 parts of distilled water, 0.1 HCl and phosphate buffer (ph 6.8) (Table 3.5). It was observed that the formulations F1, F3, F5 and F6 were found to be most stable because they do not show any precipitation or phase separation on storage in various dilution media. Self emulsified formulation F3 after dilution with distilled water is shown in Figure 3.6. Figure 3.5: Furosemide Self Emulsified formulation F3 in distilled water producing bluish tinge. Table 3.5: Observation of dilution test of FSM-SNEDDS formulations. Formulation Distilled Water 0.1N HCl Phosphate buffer ph 6.8 F1 Stable up to 6 hr Stable up to 6 hr Stable up to 6 hr F2 Unclear within 30 min Unclear within 30 min Stable up to 6 hr F3 Stable up to 6 hr Stable up to 6 hr Stable up to 6 hr F4 Stable up to 6 hr Unclear within 30 min Stable up to 6 hr F5 Stable up to 6 hr Stable up to 6 hr Stable up to 6 hr F6 Stable up to 6 hr Stable up to 6 hr Stable up to 6 hr Drug content determination FSM content of the SNEDDS formulations is shown in Table 3.6 (Results are expressed as mean±sd), which was in the limit (96 102%). Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 81
16 Table 3.6: Characterization of FSM-SNEDDS formulations Parameters F1 F2 F3 F4 F5 F6 Drug Content (%) 97.41± ± ± ± ± ±1.26 Self Emulsification 12±2 12±1 16±1 13±1 10±1 9±1 Time (s) Precipitation Stable Stable Stable Stable Unstable Unstable Clarity Bluish Bluish Bluish Bluish Turbid Turbid Viscosity (cps) 0 times dilution times dilution times dilution % Transmittance 68.48± ± ± ± ± ±0.39 Droplet Size (nm) 154.4± ± ± ± ± ±2.78 Polydispersity 0.566±0.02 1± ± ± ± ±0.02 index Zeta (mv) Potential -20.9± ± ± ± ± ± Emulsification time and precipitation assessment The rate of emulsification is an important parameter for the assessment of the efficiency or spontaneous emulsification of formulation without aid of any external thermal or mechanical energy source. Formulation should disperse completely and quickly when subjected to aqueous dilution under mild agitation of GIT due to peristaltic activity. It has been reported that self emulsification mechanism involves the erosion of a fine cloud of small droplets from the monolayer around emulsion droplets, rather than progressive reduction in droplet size (Pouton 1997). The ease of emulsification was suggested to be related to the ease of water penetration into the colloidal or gel phases formed on the surface of the droplet (Rang and Miller 1999, Groves et al., 1974). It was Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 82
17 observed that an increase in the proportion of Tween 80 from to % w/w in the composition resulted in increased self-emulsification time from 9 to 16 seconds (Table 3.6) (Results are expressed as mean±sd). This might be because of high viscosity imparted by Tween 80 which increases the free surface energy of system thereby increasing the emulsification time with increase in content of surfactant. Below 49.78% concentration of surfactant, there was turbid and unstable dispersion (Table 3.6). This may be due to excess penetration of water into the bulk oil causing massive interfacial disruption and ejection of droplets into the bulk aqueous phase (Kadu et al. 2010) Percentage transmittance (ƛ max 560 nm) The percentage transmittance of the six selected optimized formulation was determined. As the value closer to 100% is formulation which is isotropic in nature therefore, optimized formulation of F3 from S mix ratio of 4:1 gave maximum percentage transmittance (Table 3.6) (Results are expressed as mean±sd). As SNEDDS form nano emulsion in GIT, it meets with patient acceptability but isotropic nature of formulations or percentage transmittance closer to 100% gives an indication of globule size in nanometer range. The droplet size of the emulsion is a crucial factor in selfemulsification performance, because it determines the rate and extent of drug release as well as absorption (Parmar et al. 2011). Thus, the formulation has the capacity to undergo enhanced absorption and thus ability to have increased oral bioavailability Viscosity determination Viscosity of SNEDDS without dilution was found to be in between 317 and 367 cp, which was suitable for filling in hard gelatin capsule without risk of leaking problem. As SNEDDS was diluted 10 and 100 times with water, viscosity of the system was decreased, which indicates that oral administration of SNEDDS formulation will be Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 83
18 diluted with the stomach fluid and viscosity will be decreased and therefore absorption from the stomach will be fast (Table 3.6). Results are expressed as mean±sd Droplet size analysis and PDI determination The droplet size of the emulsion is an essential factor in self emulsification performance because it determines the rate and extent of drug release as well as drug absorption. Also, it has been reported that the smaller particle size of the emulsion droplets may lead to more rapid absorption and improve the bioavailability (Liu et al. 2007). It is well known that in nano emulsion systems the addition of surfactants stabilize and condense the interfacial film, while the addition of co-surfactant causes the film to expand; thus, the relative proportion of surfactant to co-surfactant has varied effects on the droplet size. From Table 3.6 (Results are expressed as mean±sd), it can be seen that formulation F3 has the smallest droplet size of 26.8 nm. Size distribution reports of formulations F1-F6 are shown in Figure Polydispersity is the ratio of standard deviation to the mean droplet size. This signifies the uniformity of droplet size within the formulation. The higher the value of polydispersity, the lower is the uniformity of the droplet size in the formulation (Dixit et al. 2010). The lowest value of polydispersity was found to be for SNEDDS formulation F3, which indicates uniformity of droplet size within the formulation. Formulation F2 has highest polydispersity value of 1, signifies non uniformity of droplets (Table 3.6) (Results are expressed as mean±sd). PDI values of more than 0.7 indicate that the sample has a very broad size distribution. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 84
19 Figure 3.6: Size distribution report of FSM-SNEDDS formulation F1. Figure 3.7: Size distribution report of FSM-SNEDDS formulation F2. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 85
20 Figure 3.8: Size distribution report of FSM-SNEDDS formulation F3. Figure 3.9: Size distribution report of FSM-SNEDDS formulation F4. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 86
21 Figure 3.10: Size distribution report of FSM-SNEDDS formulation F5. Figure 3.11: Size distribution report of FSM-SNEDDS formulation F6. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 87
22 Zeta potential determination Emulsion droplet polarity is also a very essential factor in characterizing emulsification efficiency (Shah et al. 1994). Zeta potential is the potential difference between the surface of tightly bound layer (shear plane and electroneutral region of the solution). The significance of zeta potential is that its value can be related to the stability of colloidal dispersions. Zeta potential indicates the degree of repulsion between adjacent, similarly charged particles in dispersion. For molecules and particles that are small enough, a high zeta potential will present stability. When the potential is low, attraction exceeds repulsion and the dispersion will break and flocculate. So, colloids with high zeta potential (negative or positive) are electrically stabilized. Negative values of zeta potential of the optimized formulations indicated that the formulations were negatively charged. Formulation F1 was found to be most stable formulation (Table 3.6) (Results are expressed as mean±sd). Zeta potential reports of formulation F1-F6 are shown in Figure Figure 3.12: Zeta potential report of FSM-SNEDDS formulation F1. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 88
23 Figure 3.13: Zeta potential report of FSM-SNEDDS formulation F2. Figure 3.14: Zeta potential report of FSM-SNEDDS formulation F3. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 89
24 Figure 3.15: Zeta potential report of FSM-SNEDDS formulation F4. Figure 3.16: Zeta potential report of FSM-SNEDDS formulation F5. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 90
25 Figure 3.17: Zeta potential report of FSM-SNEDDS formulation F In vitro dissolution studies SNEDDS formulation F3 showed significantly higher drug release as compared to plain FSM and marketed FSM tablet (LASIX) (Table 3.7, Figure 3.19) (Results are expressed as mean±sd). F3 showed more than 90% of drug release in 10 minutes while plain FSM and marketed tablet showed 57 and 64 %, respectively. Spontaneous formation of nanoemulsion of SNEDDS formulation F3 could be the reason for the faster rate of drug release into the aqueous medium. Dramatic increase in the rate of release of FSM from SNEDDS compared to plain FSM and marketed formulation can be attributed to its quick dispersibility and ability to keep drug in solubilized state. Thus, this greater availability of dissolved FSM from the SNEDDS formulation could lead to higher absorption and higher oral bioavailability. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 91
26 Table 3.7: In vitro dissolution studies data of plain FSM, marketed formulation and developed FSM-SNEDDS formulations. Time % Cumulative Drug Release (min) F1 F2 F3 F4 F5 F6 Plain FSM LASIX ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±1.32 Figure 3.18: In vitro dissolution studies of plain FSM, marketed formulation and developed FSM-SNEDDS formulations. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 92
27 In vitro diffusion studies Conventional dissolution testing can only provide a measure of dispersibility of SNEDDS in the dissolution medium. Alternatively, in vitro performance of SNEDDS can be evaluated by drug diffusion studies using the dialysis technique. It is very popular and well documented in many literatures (Kadu et al. 2010; Paradkar et al. 2007). SNEDDS formulations F1, F3 and F4 were selected for diffusion studies, as these formulations show smaller droplet size among other formulations. Though formulations F2, F5 and F6 has less droplet size than F1 but formulations F5 and F6 found to be unstable and turbid on precipitation and clarity test while F2 has non uniformity of droplets due to very high PDI. The release of FSM from these dosage forms was evaluated in phosphate buffer ph 6.8; the release percentage of F3 was higher than that of F1 and F4 (Table 3.8, Figure 3.20) (Results are expressed as mean±sd). It suggests that FSM dissolved perfectly in SNEDDS form and could be released due to the small droplet size, which permits a faster rate of FSM release into aqueous phase. The release rate of FSM from SNEDDS F3 (mean droplet size: 26.8 nm) was faster than SNEDDS F1 and F4 (mean droplet size: and 28.9 nm, respectively). In this study, diffusion profiles of all three formulations (F1, F3 and F4) did not show any differences during initial 1 h, however, at the end of 12 h, formulation F3 showed 98.5 % diffusion while F1 and F4 showed 86 % and 97 % diffusion, respectively (Figure 3.20). Results clearly indicate the effect of mean droplet size on FSM diffusion across dialyzing membrane. Hence decreasing the particle size of nano emulsion could increase the release rate of FSM. Therefore, F3 was selected as optimized formulation for in vivo studies having the smallest droplet size and thus higher diffusion than formulation F4. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 93
28 Table 3.8: In vitro diffusion studies data of FSM-SNEDDS F1, F3 and F4. Time (Hrs) % Diffusion F1 F3 F ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±2.09 Figure 3.19: In vitro diffusion studies of FSM-SNEDDS F1, F3 and F4. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 94
29 In vivo pharmacodynamic studies This study was performed to evaluate the pharmacodynamic potential of an optimized formulation (F3) against plain FSM. Cumulative volumes of excreted urine after oral administration compounds are shown in Figure 3.21A (Table 3.9). Statistically significant diuretic effect of SNEDDS was observed after 180 minutes in comparison to FSM, control and placebo. Sodium and chloride ions quantification is one of the best methods to determine diuretic effect of drugs (Opie and Kaplan 1991; Field et al. 1984). Values of concentration of sodium in excreted urine are shown in Figure 3.21B (Table 3.9). SNEDDS group showed significant increase in the amounts of electrolyte in comparison to control and placebo groups after 120 minutes of administration. However, effect on sodium concentration by SNEDDS was more but not statistically significant as compared to FSM group. Table 3.9: Time course of urine and sodium output in different groups. Values are reported as mean ± S.E.M. for twelve rats in each group. Time Control Placebo FSM SNEDDS (min) Cumulative Sodium Cumulative Sodium Cumulative Sodium Cumulative Sodium Urine Concentration Urine Concentration Output (µl)x10 4 (meq/l) X10 2 Output (µl) X10 4 (meq/l) X10 2 Urine Output Concentration Urine Concentration (µl)x10 4 (meq/l) X10 2 Output (meq/l) X10 2 (µl)x ± ± ± ±0.25 1± ± ± ± ± ± ± ± ± ± ±0.14** 1.18±0.01** 180 2± ± ± ± ±0.16** 1.22± ±0.35 *** ± ± ± ± ±0.37** 1.39±0.02** 8.52±0.41 *** **Statistically significant from control and placebo group. p< ±0.010** 1.67±0.02** ***Statistically significant from control, placebo and FSM group. p<0.05 Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 95
30 Figure 3.20: (A) Time course of urine output in different groups. (B) Time course of sodium output in different groups. Values are reported as mean ± S.E.M. for twelve rats in each group. **Statistically significant from control and placebo group. p<0.05 ***Statistically significant from control, placebo and FSM group. p<0.05 Diuretic activity data suggest that SNEDDS formulation increased the pharmacological effect of FSM. The higher diuretic activity of the SNEDDS is due to complete dissolution of FSM in SNEDDS, which could have increased absorption. Solubility is a crucial characteristic for increasing the bioavailability of drugs according to the BCS (Amidon et al. 1995). Moreover, SNEDDS play an important role in the improvement of permeability too. Higher permeability may be attributed to Capmul MCM, Tween 80 and Transcutol P as these components have the ability to enhance the permeability (Date et al. 2010; Singh et al. 2009; Porter et al. 2008; Tang et al. 2007). However the present work did not deal with the permeation experiments using cell models and this aspect will be developed in future studies Stability studies Optimized SNEDDS formulation (F3) filled into hard gelatin capsules as the final dosage form. Liquid-filled hard gelatin capsules are prone to leakage and the entire system has a very limited shelf life owing to its liquid characteristics and the possibility Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 96
31 of precipitation of the FSM from the system. Thus, to evaluate its stability and the integrity of the dosage form, the optimized formulation (F3) was subjected to stability studies. No change in the physical parameters such as homogeneity and clarity was observed during the stability studies. There was no major change in the FSM content, drug release (t 90% ) and % transmittance. It was also observed that the formulation was compatible with the hard gelatin capsule shells. Also, there was no phase separation and drug precipitation was found at the end of three-month stability studies indicating that FSM remained chemically stable in SNEDDS (Table 3.10) (Results are expressed as mean±sd). Table 3.10: Evaluation data of FSM-SNEDDS formulation subjected to stability studies. Sampling Points (Days) % Drug Content t 90% (min) % Transmittance ±1.58 < ±1.46 < ±1.77 < ±2.02 < Conclusions SNEDDS was successfully emerged as appealing approach to improve the bioavailability of furosemide. Increased solubility, Increased dissolution rate and ultimately increased bioavailability of a poorly water-soluble drug, furosemide, was observed with an optimized SNEDDS formulation consisting of Capmul MCM (18.67 % w/w), Tween 80 (59.73 % w/w), Transcutol P (14.93 % w/w) and FSM (6.67 % w/w). The developed formulation showed higher pharmacodynamic potential as compared with plain FSM. Results from stability studies established the stability of the developed formulation. Therefore, our study confirmed that the SNEDDS formulation Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 97
32 can be used as a possible alternative to traditional oral formulations of FSM to improve its bioavailability. Design Development & Evaluation of SEDDS for Poorly Water Soluble Drugs 98
5. Formulation and Development of Microemulsion and SMEDDS
5. Formulation and Development of Microemulsion and SMEDDS Contents 5 Formulation and Development of Microemulsion and SMEDDS. 142 5.1 Formulation techniques for Microemulsion... 142 5.1.1 Phase titration
More informationCinnarizine loaded lipid based system: preparation, optimization and in-vitro evaluation
IOSR Journal of Pharmacy ISSN: 2250-3013, www.iosrphr.org Volume 2 Issue 5 Sep-Oct. 2012 PP.47-56 Cinnarizine loaded lipid based system: preparation, optimization and in-vitro evaluation Shubham Rai 1,
More informationENHANCEMENT OF SOLUBILITY OF BICALUTAMIDE DRUG USING SOLID DISPERSION TECHNIQUE
PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES ENHANCEMENT OF SOLUBILITY OF BICALUTAMIDE DRUG USING SOLID DISPERSION TECHNIQUE Kantilal B. Narkhede *1, R. B. Laware 2, Y. P.
More informationJournal of Chemical and Pharmaceutical Research, 2012, 4(8): Research Article
Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2012, 4(8):3914-3919 Research Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 Novel Self Micro-emulsifying Drug Delivery Systems
More informationTHE INFLUENCE OF OILS AND SURFACTANTS ON THE FORMATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEMS (SNEDDS) CONTAINING THERAPEUTIC PROTEIN
MATERIALS SCIENCE and TECHNOLOGY Edited by Evvy Kartini et.al. THE INFLUENCE OF OILS AND SURFACTANTS ON THE FORMATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEMS (SNEDDS) CONTAINING THERAPEUTIC PROTEIN
More informationFORMULATION AND CHARACTERIZATION OF TELMISATAN SOLID DISPERSIONS
International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 974-434 Vol.2, No.1, pp 341-347, Jan-Mar 1 FORMULATION AND CHARACTERIZATION OF TELMISATAN SOLID DISPERSIONS Kothawade S. N. 1 *, Kadam
More informationDEVELOPMENT AND CHARACTERIZATION OF SELF EMULSIFYING DRUG DELIVERY SYSTEM OF A POORLY WATER SOLUBLE DRUG USING NATURAL OIL
Acta Poloniae Pharmaceutica ñ Drug Research, Vol. 69 No. 4 pp. 713ñ717, 2012 ISSN 0001-6837 Polish Pharmaceutical Society PHARMACEUTICAL TECHNOLOGY DEVELOPMENT AND CHARACTERIZATION OF SELF EMULSIFYING
More informationThe Nitrofurantoin Capsules Revision Bulletin supersedes the currently official monograph.
Nitrofurantoin Capsules Type of Posting Revision Bulletin Posting Date 28 Dec 2018 Official Date 01 Jan 2019 Expert Committee Chemical Medicines Monographs 1 Reason for Revision Compliance In accordance
More informationPelagia Research Library
Available online at www.pelagiaresearchlibrary.com Der Pharmacia Sinica, 2013, 4(6):48-58 Development of self micro emulsifying drug delivery system: Application to pimozide delivery ISSN: 0976-8688 CODEN
More informationVolume 13, Issue 2, March April 2012; Article-020 FORMULATION AND EVALUATION OF SOLID SELF EMULSIFYING DRUG DELIVERY SYSTEM FOR LIPOPHILLIC DRUG
ISSN 976 44X Research Article FORMULATION AND EVALUATION OF SOLID SELF EMULSIFYING DRUG DELIVERY SYSTEM FOR LIPOPHILLIC DRUG Snehal G. Dhomne, Swapnil B. Ajabale, G.S. Bhoyar Smt. Kishoritai Bhoyar College
More informationFormulation and Evaluation of Furosemide Solid Self-emulsifying Drug Delivery System
ORIGINAL ARTICLE Formulation and Evaluation of Furosemide Solid Self-emulsifying Drug Delivery System J. Renuka 1, Y. Ganesh Kumar 2, D. Saritha 3, V. Mahesh 4 1,4 Department of Pharmaceutics, Vikas College
More informationSelf-microemulsifying drug delivery system (SMEDDS) is a promising system for the Biopharmaceutics Classification
AJP R_AP done on ORIGINAL ARTICLE Formulation and development of self-microemulsifying drug delivery system of pioglitazone hydrochloride Jyotsana R. Madan,, Bandavane Sudarshan, Vinod S. Kadam, Dua Kamal
More informationParidhi et al., ARPB, 2012; Vol 2 (IV) ISSN
FORMULATION AND IN-VITRO CHARACTERIZATION OF SELF EMULSIFYING DRUG DELIVERY SYSTEM OF CISAPRIDE *P. Porwal 1, S. Bhargava 1, R.S. Bhaduria 1, S.S. Shukla 2 and S.J. Daharwal 3 1Shrinathji Institute of
More informationEvaluation of combination drugs before the development of self-emulsifying drug delivery system
RESEARCH ARTICLE Evaluation of combination drugs before the development of self-emulsifying drug delivery system Nidhi Sharma 1, Ved Prakash 2, Saurabh Mann 1, Roop K. Khar 1 1 Department of Pharmaceutics,
More informationFORMULATION AND EVALUATION OF MICROEMULSION BASED GEL OF CLOTRIMAZOLE
268 P a g e International Standard Serial Number (ISSN): 2319-8141 International Journal of Universal Pharmacy and Bio Sciences 3(3): May-June 2014 INTERNATIONAL JOURNAL OF UNIVERSAL PHARMACY AND BIO SCIENCES
More informationSOLUBILITY ENHANCEMENT OF AZILSARTAN BY SELF- EMULSIFYING LIPID FORMULATIONS
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES Reddy et al. S SJIF Impact Factor 6.647 Volume 6, Issue 3, 957-974 Research Article ISSN 2278 4357 SOLUBILITY ENHANCEMENT OF AZILSARTAN BY SELF- EMULSIFYING
More informationChemate and Chowdary, IJPSR, 2012; Vol. 3(7): ISSN:
IJPSR (2012), Vol. 3, Issue 07 (Research Article) Received on 18 March, 2012; received in revised form 25 April, 2012; accepted 22 June, 2012 A FACTORIAL STUDY ON ENHANCEMENT OF SOLUBILITY AND DISSOLUTION
More informationA FACTORIAL STUDY ON THE ENHANCEMENT OF DISSOLUTION RATE OF KETOPROFEN BY SOLID DISPERSION IN COMBINED CARRIERS
Research Article A FACTORIAL STUDY ON THE ENHANCEMENT OF DISSOLUTION RATE OF KETOPROFEN BY SOLID DISPERSION IN COMBINED CARRIERS K. P. R. Chowdary *, Tanniru Adinarayana, T. Vijay, Mercy. R. Prabhakhar
More informationBiopharmaceutics Dosage form factors influencing bioavailability Lec:5
Biopharmaceutics Dosage form factors influencing bioavailability Lec:5 Ali Y Ali BSc Pharmacy MSc Industrial Pharmaceutical Sciences Dept. of Pharmaceutics School of Pharmacy University of Sulaimani 09/01/2019
More informationSTUDIES ON EFFECT OF BINDERS ON ETORICOXIB TABLET FORMULATIONS
Int. J. Chem. Sci.: 10(4), 2012, 1934-1942 ISSN 0972-768X www.sadgurupublications.com STUDIES ON EFFECT OF BINDERS ON ETORICOXIB TABLET FORMULATIONS K. VENUGOPAL * and K. P. R. CHOWDARY a Nirmala College
More informationCHAPTER VI FACTORIAL STUDIES ON THE EFFECTS OF CYCLODEXTRINS AND SOLUTOL HS15 ON THE SOLUBILITY AND DISSOLUTION RATE OF EFAVIRENZ AND RITONAVIR
CHAPTER VI FACTORIAL STUDIES ON THE EFFECTS OF CYCLODEXTRINS AND SOLUTOL HS15 ON THE SOLUBILITY AND DISSOLUTION RATE OF EFAVIRENZ AND RITONAVIR Efavirenz and ritonavir, two widely prescribed anti retroviral
More informationDevelopment of Self Emulsifying Drug Delivery System: Application to Fenofibrate Delivery
Research Article Packiaraj Jeyachandran Manohari 1*, Janakiraman Kunchitapatham 1, Venkateswaran Chidambaram Seshadri 1 1 Department of Pharmacy, Annamalai University, Annamalai Nagar, Chidambaram, Tamil
More informationSTABILITY STUDIES OF FORMULATED CONTROLLED RELEASE ACECLOFENAC TABLETS
Int. J. Chem. Sci.: 8(1), 2010, 405-414 STABILITY STUDIES OF FORMULATED CONTROLLED RELEASE ACECLOFENAC TABLETS V. L. NARASAIAH, T. KARTHIK KUMAR, D. SRINIVAS, K. SOWMYA, P. L. PRAVALLIKA and Sk. Md. MOBEEN
More informationA FACTORIAL STUDY ON ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF IBUPROFEN BY β CYCLODEXTRIN AND SOLUTOL HS15
INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY Available online at www.ijrpc.com Research Article A FACTORIAL STUDY ON ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF IBUPROFEN BY β CYCLODEXTRIN
More informationCompliance. Should you have any questions, please contact Behnaz Almasi, Associate Scientific Liaison ( or
Extended-Release Tablets Type of Posting Revision Bulletin Posting Date 30 Mar 2018 Official Date 01 Apr 2018 Expert Committee Chemical Medicines Monographs 3 Reason for Revision Compliance In accordance
More informationSelf-microemulsifying drug delivery system for enhancement of oral bioavailability of losartan
Research Article Self-microemulsifying drug delivery system for enhancement of oral bioavailability of losartan Pawar Anil R 1,2 *, Chaudhari Pravin D 3 ABSTRACT Objective: The objective of the present
More informationResearch Article [Gupta et al., 2(3): March, 2011] ISSN:
Research Article [Gupta et al., 2(3): March, 211] INTERNATIONAL JOURNAL OF PHARMACY & LIFE SCIENCES Preparation and in-vitro evaluation of self emulsifying drug delivery system of antihypertensive drug
More informationPreparation and Characterization of Candesartan Cilexetil Solid Lipid Nanoparticulate Capsules
Research Article Preparation and Characterization of Candesartan Cilexetil Solid Lipid Nanoparticulate Capsules *Surya Kiran Vuddisa, Subramanian S., Sindhu Raavi Department of Pharmaceutics, PSG College
More informationDEVELOPMENT OF SOLID LIPID NANOPARTICLES OF A WATER SOLUBLE DRUG
Page4813 Indo American Journal of Pharmaceutical Research, 2016 ISSN NO: 2231-6876 DEVELOPMENT OF SOLID LIPID NANOPARTICLES OF A WATER SOLUBLE DRUG Akkshata Parab*, Amrita Bajaj Department of Pharmaceutics,
More informationMEDAK DIST. ANDHRA PRADESH STATE, INDIA. Research Article RECEIVED ON ACCEPTED ON
Page67 Available Online through IJPBS Volume 1 Issue 2 APRIL- JUNE 2011 SIMPLE QUANTITATIVE METHOD DEVELOPMENT AND VALIDATION OF VALSARTAN IN PUREFORM AND PHARMACEUTICAL DOSAGE FORMS BYUV SPECTROSCOPY
More informationFORMULATION DEVELOPMENT AND IN-VITRO EVALUATION OF SOLID AND LIQUID SELF EMULSIFYING DRUG DELIVERY SYSTEM OF POORLY WATER SOLUBLE DRUG KETOPROFEN
Page6565 Indo American Journal of Pharmaceutical Research, 2016 ISSN NO: 2231-6876 FORMULATION DEVELOPMENT AND IN-VITRO EVALUATION OF SOLID AND LIQUID SELF EMULSIFYING DRUG DELIVERY SYSTEM OF POORLY WATER
More informationTENOFOVIR TABLETS: Final text for addition to The International Pharmacopoeia (June 2010)
June 2010 TENOFOVIR TABLETS: Final text for addition to The International Pharmacopoeia (June 2010) This monograph was adopted at the Forty-fourth WHO Expert Committee on Specifications for Pharmaceutical
More informationINTERNATIONAL JOURNAL OF INSTITUTIONAL PHARMACY AND LIFE SCIENCES
International Journal of Institutional Pharmacy and Life Sciences 4(2): March-April 2014 INTERNATIONAL JOURNAL OF INSTITUTIONAL PHARMACY AND LIFE SCIENCES Pharmaceutical Sciences Review Article!!! Received:
More informationThis revision also necessitates a change in the table numbering in the test for Organic Impurities.
Methylphenidate Hydrochloride Extended-Release Tablets Type of Posting Notice of Intent to Revise Posting Date 27 Jul 2018 Targeted Official Date To Be Determined, Revision Bulletin Expert Committee Chemical
More informationFormulation and characterization of pioglitazone HCl self emulsifying drug delivery system
Available online at www.scholarsresearchlibrary.com Scholars Research Library Der Pharmacia Lettre, 2013, 5 (2):292-305 (http://scholarsresearchlibrary.com/archive.html) ISSN 0975-5071 USA CODEN: DPLEB4
More informationEmulsions. Purpose of emulsions and of emulsification:
Pharmacist Ghada Hamid Emulsions Emulsion is a dispersion in which the dispersed phase is composed of small globules of a liquid distributed throughout a vehicle in which it is immiscible. The dispersed
More informationDEVELOPMENT AND VALIDATION OF COLORIMETRIC METHODS FOR THE DETERMINATION OF RITONAVIR IN TABLETS
Int. J. Chem. Sci.: 8(1), 2010, 711-715 DEVELOPMENT AND VALIDATION OF COLORIMETRIC METHODS FOR THE DETERMINATION OF RITONAVIR IN TABLETS R. PRIYADARSINI *, V. NIRAIMATHI, T. SARASWATHY, V. GOPI and R.
More information7. SUMMARY, CONCLUSION AND RECOMMENDATIONS
211 7. SUMMARY, CONCLUSION AND RECOMMENDATIONS Drug absorption from the gastro intestinal tract can be limited by various factors with the most common one being poor aqueous solubility and poor permeability
More informationResearch Article Derivative Spectrophotometric Method for Estimation of Metformin Hydrochloride in Bulk Drug and Dosage Form
Research Article Derivative Spectrophotometric Method for Estimation of Metformin Hydrochloride in Bulk Drug and Dosage Form Gowekar NM, Lawande YS*, Jadhav DP, Hase RS and Savita N. Gowekar Department
More informationSolid self-emulsifying drug delivery system of Furosemide
Abstract Solid self-emulsifying drug delivery system of Furosemide Bhupendra G Prajapati 1, Hitesh Patel 1, Shruti Rao 2 1 Shree S.K. Patel College of Pharmaceutical Education & Research, Ganpat University,
More informationDevelopment and Evaluation of Solid Self Nano- Emulsifying Formulation of Rosuvastatin Calcium for Improved Bioavailability
Tropical Journal of Pharmaceutical Research April 2015; 14 (4): 575-582 ISSN: 1596-5996 (print); 1596-9827 (electronic) Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001
More informationFormulation and Evaluation of Acyclovir Liposomes
Krishna Mohan Chinnala and Rabinarayan Panigrahy., 217/ Formulation and evaluation of acyclovir RESEARCH ARTICLE International Research Journal of Pharmaceutical and Biosciences Pri -ISSN: 2394-5826 http://www.irjpbs.com
More informationAsian Journal of Pharmacy and Life Science ISSN Vol. 2 (2), July-Sept,2012
STUDIES ON EFFECT OF SUPERDISINTEGRANTS ON ETORICOXIB TABLET FORMULATIONS Chowdary K. P. R 1, Venugopal. K *2 1 College of Pharmaceutical Sciences, Andhra University, Vishakapattanam. 2 * Nirmala college
More information>>> Oral Formulation Optimization. Introduction. A Tiered Approach for Identifying Enabling Formulations
Application Note #28-DMPK-3 >>> Oral Formulation Optimization Introduction Among the criteria required of compounds advancing from drug discovery programs, adequate systemic exposure (plasma concentrations
More informationFormulation and Evaluation of Simvastatin SEDDS
Formulation and Evaluation of Simvastatin SEDDS Prajapati Paresh A 1. Maheshwari Mittal M. 2 *, 1. Department of Pharmaceutics, Shankersinh Vaghela Bapu Institute of Pharmacy, Vasana, Gandhinagar, Gujarat,
More informationA STUDY ON SUITABILITY OF NIMESULIDE-BETACYCLODEXTRIN COMPLEX IN ORAL AND TOPICAL DOSAGE FORMS
International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 1, Suppl 1, Nov.-Dec. 2009 Research Article A STUDY ON SUITABILITY OF NIMESULIDE-BETACYCLODEXTRIN COMPLEX IN ORAL AND TOPICAL DOSAGE
More informationResidue Monograph prepared by the meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), 82 nd meeting 2016.
Residue Monograph prepared by the meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), 82 nd meeting 2016 Aspartame This monograph was also published in: Compendium of Food Additive
More informationRITONAVIRI COMPRESSI RITONAVIR TABLETS. Final text for addition to The International Pharmacopoeia (July 2012)
July 2012 RITONAVIRI COMPRESSI RITONAVIR TABLETS Final text for addition to The International Pharmacopoeia (July 2012) This monograph was adopted at the Forty-sixth WHO Expert Committee on Specifications
More informationINTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH AND BIO-SCIENCE SELF EMULSIFYING DRUG DELIVERY SYSTEM (SEDDS): A REVIEW
REVIEW ARTICLE INTERNATIONAL JOURNAL OF PHARMACEUTICAL RESEARCH AND BIO-SCIENCE A Path for Horizing Your Innovative Work SELF EMULSIFYING DRUG DELIVERY SYSTEM (SEDDS): A REVIEW *NITESH SOLANKI, SNEHAL
More informationFACTORIAL STUDIES ON THE EFFECTS OF HYDROXY PROPYL β- CYCLODEXTRIN AND POLOXAMER 407 ON THE SOLUBILITY AND DISSOLUTION RATE OF BCS CLASS II DRUGS
JChrDD Vol 2 Issue 2 2011: 89-93 ISSN 2249-6785 Journal of Chronotherapy and Drug Delivery Received: August 06, 2011 Accepted: Sep 12, 2011 Original Research Paper FACTORIAL STUDIES ON THE EFFECTS OF HYDROXY
More informationSELF-EMULSIFYING DRUG DELIVERY SYSTEMS: A REVIEW
SELF-EMULSIFYING DRUG DELIVERY SYSTEMS: A REVIEW Jamilur Reza* Department of Pharmacy University of Science and Technology Chittagong Abstract Self-emulsifying drug delivery systems (SEDDS) possess unparalleled
More informationEFFECT OF PVP ON CYCLODEXTRIN COMPLEXATION OF EFAVIRENZ FOR ENHANCING ITS SOLUBILITY AND DISSOLUTION RATE
INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY Available online at www.ijrpc.com Research Article EFFECT OF PVP ON CYCLODEXTRIN COMPLEXATION OF EFAVIRENZ FOR ENHANCING ITS SOLUBILITY AND DISSOLUTION
More informationFormulation and Evaluation of SEDDS containing lipid lowering Drug
Formulation and Evaluation of SEDDS containing lipid lowering Drug Maheshwari Mittal M. 1 *, Prajapati Paresh A. 2 Research Scholar, JJT University, Jhunjhunu, Rajasthan, India Department of Pharmaceutics,
More informationDesign and Evaluation of Self-Micro Emulsifying Drug Delivery Systems (SMEDDS) of Cefuroxime Axetil
Research Article Design and Evaluation of Self-Micro Emulsifying Drug Delivery Systems (SMEDDS) of Cefuroxime Axetil Satish Puttachari a, *, Navanath. V. Kalyane b, Sarbani Duttagupta c a Department of
More informationMixed Hydrotropy: Novel Science of Solubility Enhancement
Research Paper Mixed Hydrotropy: Novel Science of Solubility Enhancement R. K. MAHESHWARI* AND Y. JAGWANI Shri G. S. Institute of Technology and Science, 23-Park Road, Indore-452 003, Madhya Pradesh, India
More informationIJRPC 2011, 1(4) Rohan et al. ISSN: INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY
INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY Available online at www.ijrpc.com Research Article ABSORPTION CORRECTION METHOD AND SIMULTANEOUS EQUATION METHOD FOR THE SIMULTANEOUS ESTIMATION
More informationSELF-EMULSIFYING DRUG DELIVERY SYSTEM: A NOVEL DRUG DELIVERY SYSTEM
http://www.ijapbr.com/ International journal of Applied Pharmaceutical and Biological Research, 2017; 2(3):76-83 Review Article ISSN : 2456-0189 SELF-EMULSIFYING DRUG DELIVERY SYSTEM: A NOVEL DRUG DELIVERY
More informationDepartment of Pharmacy, University of Asia Pacific, Road # 5 A, House # 73, Dhanmondi, Dhaka-1209, Bangladesh
IJPSR (2012), Vol. 3, Issue 03 (Research Article) Received on 19 November, 2011; received in revised form 24 December, 2011; accepted 23 February, 2012 IN VITRO STUDY OF SELF EMULSIFYING DRUG DELIVERY
More informationComparative Dissolution Study of Glipizide by Solid Dispersion Technique
Comparative Dissolution Study of Glipizide by Solid Dispersion Technique Dehghan M H G 1, Saifee M 1, Hanwate R M 2 1 Y.B.Chavan College of Pharmacy,Dr. Rafiq Zakaria campus, Aurangabad-431001, Maharashtra,
More information3.1 Background. Preformulation Studies
Preformulation Studies 3.1 Background Delivery of any drug requires a suitable dosage form to get optimum therapeutic effects. The development of such dosage forms fundamental properties of the drug molecule
More informationAvailable Online through Research Article
ISSN: 0975-766X Available Online through Research Article www.ijptonline.com DESIGN AND EVALUATION OF GASTRORETENTIVE TABLETS FOR CONTROLLED DELIVERY OF NORFLOXOCIN Ganesh Kumar Gudas*, Subal Debnath,
More informationformulation John K. Tillotson Abitec (SENDS)
As appeared in July 217 Tablets & Capsules www.tabletscapsules.com formulation An introduction to self-emulsifying nutraceutical delivery systems (SENDS) John K. Tillotson Abitec Like their counterparts
More informationAvailable Online through Research Article
ISSN: 0975-766X Available Online through Research Article www.ijptonline.com SPECTROPHOTOMETRIC METHODS FOR THE DETERMINATION OF FROVATRIPTAN SUCCINATE MONOHYDRATE IN BULK AND PHARMACEUTICAL DOSAGE FORMS
More informationTransdermal Delivery of Newer Atypical Antipsychotics ABSTRACT
Transdermal Delivery of Newer Atypical Antipsychotics ABSTRACT Abstract Risperidone and olanzapine, newer atypical antipsychotics are highly effective and safer in the treatment of psychosis. A low dose
More informationPreparation and Evaluation of Ethyl Cellulose Coated Microcapsules of Carbamazepine for Controlled Release
Asian Journal of Chemistry Vol. 20, No. 8 (2008), 5901-5907 Preparation and Evaluation of Ethyl Cellulose Coated Microcapsules of Carbamazepine for Controlled Release K.P.R. CHOWDARY* and MALLURU SUBBA
More informationA FACTORIAL STUDY ON THE ENHANCEMENT OF DISSOLUTION RATE OF ACECLOFENAC BY SOLID DISPERSION IN STARCH PHOSPHATE AND GELUCIRE
INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY Available online at www.ijrpc.com Research Article A FACTORIAL STUDY ON THE ENHANCEMENT OF DISSOLUTION RATE OF ACECLOFENAC BY SOLID DISPERSION
More informationDevelopment and Validation of a UV-Spectrophotometric Method for Quantification of Atorvastatin in Tablets
Journal of PharmaSciTech 0; ():4-40 Research Article Development and Validation of a UV-Spectrophotometric Method for Quantification of Atorvastatin in Tablets Ghanty S*, Sadhukhan N, Mondal A Gupta College
More informationFormulation Development of Aceclofenac Tablets Employing Starch Phosphate -A New Modified Starch
Abstract K.P.R. Chowdary et al. / International Journal of Pharma Sciences and Research (IJPSR) Formulation Development of Aceclofenac Tablets Employing Starch Phosphate -A New Modified Starch K.P.R. Chowdary*,
More informationA Comparative Evaluation of Cross Linked Starch Urea-A New Polymer and Other Known Polymers for Controlled Release of Diclofenac
Asian Journal of Chemistry Vol. 22, No. 6 (2010), 4239-4244 A Comparative Evaluation of Cross Linked Starch Urea-A New Polymer and Other Known Polymers for Controlled Release of Diclofenac K.P.R. CHOWDARY*
More informationENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF NIMESULIDE BY CYCLODEXTRINS, POLOXAMER AND PVP
Int. J. Chem. Sci.: 9(2), 20, 637-646 ISSN 0972-768X www.sadgurupublications.com ENHANCEMENT OF SOLUBILITY AND DISSOLUTION RATE OF NIMESULIDE BY CYCLODEXTRINS, POLOXAMER AND PVP K. P. R. CHOWDARY *, K.
More informationVol - 4, Issue - 4, Supl 1, Sept 2013 ISSN: Chauhan et al PHARMA SCIENCE MONITOR
PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES KETOCONAZOLE LOADED SOLID SELF EMULSIFYING DRUG DELIVERY SYSTEM: FORMULATION AND IN-VITRO CHARACTERIZATION S. P. Chauhan*, A.
More informationFormulation and Evaluation of Solid lipid nanoparticles: Isoniazid
129 Research Article Formulation and Evaluation of Solid lipid nanoparticles: Isoniazid Umatiya Imran*, Chintan Aundhia, A.K.Seth, Sachin Chauhan, Nirmal Shah Department of pharmacy, Sumandeep Vidhyapeeth
More informationRevision Bulletin 28 Jul Aug 2017 Chemical Medicines Monographs 3
Oxybutynin Chloride Extended-Release Tablets Type of Posting Posting Date Official Date Expert Committee Reason for Revision Revision Bulletin 28 Jul 2017 01 Aug 2017 Chemical Medicines Monographs 3 Compliance
More informationRinku Verma*, G.N. Darwhekar, Ashish Gupta and Praveen Sharma Acropolis Institute of Pharmaceutical Education and Research, Indore, MP, India
INTERNATIONAL JOURNAL OF PHARMACY & LIFE SCIENCES (Int. J. of Pharm. Life Sci.) Design and development of microemulsion drug delivery system of felodipine for improvement of oral bioavailability Rinku
More informationDevelopment of Solid SEDDS, V: Compaction and Drug Release Properties of Tablets Prepared by Adsorbing Lipid-Based Formulations onto Neusilin US2
Pharm Res (2013) 30:3186 3199 DOI 10.1007/s11095-013-1106-4 RESEARCH PAPER Development of Solid SEDDS, V: Compaction and Drug Release Properties of Tablets Prepared by Adsorbing Lipid-Based Formulations
More informationARTESUNATE TABLETS: Final text for revision of The International Pharmacopoeia (December 2009) ARTESUNATI COMPRESSI ARTESUNATE TABLETS
December 2009 ARTESUNATE TABLETS: Final text for revision of The International Pharmacopoeia (December 2009) This monograph was adopted at the Forty-fourth WHO Expert Committee on Specifications for Pharmaceutical
More informationSpectrophotometric Method for Estimation of Sitagliptin Phosphate in Bulk...
Spectrophotometric Method for Estimation of Sitagliptin Phosphate in Bulk... I J P F A International Science Press Spectrophotometric Method for Estimation of Sitagliptin Phosphate in Bulk and Tablet Dosage
More informationFormulation and Evaluation of Self microemulsifying drug delivery system of low solubility drug for enhanced solubility and dissolution
Page7 e-issn 2249-622X RESEARCH ARTICLE Formulation and Evaluation of Self microemulsifying delivery system of low solubility for enhanced solubility and dissolution Divyakumar Bora, Priyanka Borude, Kiran
More informationcontents of the monograph in effect today. Please refer to the current edition of the USP NF for official text.
Metoprolol Succinate Extended-Release Tablets Type of Posting Notice of Intent to Revise Posting Date 26 Jan 2018, revised 12 Feb 2018 1 Targeted Official Date To Be Determined, Revision Bulletin Expert
More informationIJPAR Vol.3 Issue 4 Oct-Dec-2014 Journal Home page:
IJPAR Vol.3 Issue 4 Oct-Dec-2014 Journal Home page: ISSN: 2320-2831 Research article Open Access Method development and validation of tenofovir disoproxil fumerate and emtricitabine in combined tablet
More informationENHANCEMENT OF SOLUBILITY, DISSOLUTION RATE AND BIOAVAILABILITY OF RITONAVIR BY CYCLODEXTRINS AND SOLUTOL HS15 - A FACTORIAL STUDY
INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY Available online at www.ijrpc.com Research Article ENHANCEMENT OF SOLUBILITY, DISSOLUTION RATE AND BIOAVAILABILITY OF RITONAVIR BY CYCLODEXTRINS
More informationFormulation and Assessment of Lipid Based Formulation of Olmesartan Medoxomil
International Journal of Drug Development & Research July-September 2011 Vol. 3 Issue 3 ISSN 0975-9344 Available online http://www.ijddr.in Covered in Official Product of Elsevier, The Netherlands 2010
More informationSIMULTANEOUS ESTIMATION OF VALSARTAN AND HYDROCHLOROTHIAZIDE IN TABLETS BY RP-HPLC METHOD
170 Original Article SIMULTANEOUS ESTIMATION OF VALSARTAN AND HYDROCHLOROTHIAZIDE IN TABLETS BY RP-HPLC METHOD *Lakshmana Rao A, 1 Bhaskara Raju V *V.V. Institute of Pharmaceutical Sciences, Gudlavalleru,
More informationMadadi Sunitha Reddy & Mallika Banu. Int. Res. J. Pharm. 2017, 8 (12) INTERNATIONAL RESEARCH JOURNAL OF PHARMACY
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY www.irjponline.com ISSN 2230 8407 Research Article FORMULATION AND IN-VITRO EVALUATION OF FENOFIBRATE DRY EMULSION IN HARD VEGETARIAN CAPSULES Madadi Sunitha
More informationpharmaceutical formulations. Anagliptin shows absorption maximum at 246 nm and obeys beer s law in the
ISSN: 0975-766X CODEN: IJPTFI Available Online through Research Article www.ijptonline.com DEVELOPMENT AND VALIDATION OF ANALYTICAL METHOD FOR ESTIMATION OF ANAGLIPTIN IN TABLET DOSAGE FORM BY U.V. SPECTROPHOTOMETRIC
More informationValidated UV Spectrophotometric Method Development And Stability Studies Of Acamprosate Calcium In Bulk And Tablet Dosage Form
International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.5, No.3, pp 1241-1246, July-Sept 2013 Validated UV Spectrophotometric Method Development And Stability Studies Of Acamprosate
More informationLABORATORY MANUAL PHM 2143 PHYSICAL PHARMACY II
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY LABORATORY MANUAL PHM 2143 PHYSICAL PHARMACY II NAME MATRIC NO. Please read the instructions, carry out the lab practical and answer the questions. You may be requested
More informationDEVELOPMENT AND CHARACTERIZATION OF TOPICAL MICROEMULSION OF LEVOFLOXACIN
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES Volume 2, Issue 6, 5935-5947. Research Article ISSN 2278 4357 DEVELOPMENT AND CHARACTERIZATION OF TOPICAL MICROEMULSION OF LEVOFLOXACIN S.K. Prajapati,
More informationDevelopment and Validation of a New Uv Method for the Analysis of Rebamipide
International Journal of PharmTech Research CODEN (USA): IJPRIF ISSN : 0974-4304 Vol.3, No.3, pp1270-1274, July-Sept 2011 Development and Validation of a New Uv Method for the Analysis of Rebamipide Praveen
More informationPetrolatum. Stage 4, Revision 1. Petrolatum is a purified semi solid mixture of hydrocarbons obtained from petroleum.
1 001-1208PDG.pdf Petrolatum Stage 4, Revision 1 Definition Petrolatum is a purified semi solid mixture of hydrocarbons obtained from petroleum. It may contain a suitable antioxidant. Description and Solubility
More informationChange to read: BRIEFING
BRIEFING Dibasic Calcium Phosphate Dihydrate, USP 29 page 359. The Japanese Pharmacopoeia is the coordinating pharmacopeia for the international harmonization of the compendial standards for the Dibasic
More informationLecipro AOCS Lecithin SC Montreal
Lecithin Dispersion and Emulsification Demo W. van Nieuwenhuyzen Lecipro Consulting www.lecipro.nl AOCS Lecithin SC - Montreal, April 27-28, 28, 2013 Lecipro AOCS Lecithin SC Montreal 2013 1 Topics Emulsifying
More informationTramadol Hydrochloride Extended-Release Tablets. Expert Committee Chemical Medicines Monographs 2 Reason for Revision Compliance
Tramadol Hydrochloride Extended-Release Tablets Type of Posting Revision Bulletin Posting Date 27 May 2016 Official Date 01 Jun 2016 Expert Committee Chemical Medicines Monographs 2 Reason for Revision
More informationDevelopment, Estimation and Validation of Lisinopril in Bulk and its Pharmaceutical Formulation by HPLC Method
ISSN: 0973-4945; CODEN ECJAO E- Chemistry http://www.e-journals.net 2012, 9(1), 340-344 Development, Estimation and Validation of Lisinopril in Bulk and its Pharmaceutical Formulation by PLC Method V.
More information6.02 Uniformity of Dosage Units
6.02 Uniformity of Dosage Units Change 1. Content Uniformity, 3. Criteria and Table 6.02-2 as follows: 1. Content Uniformity Select not less than 30 units, and proceed as follows for the dosage form designated.
More informationInternational Journal of Research in Pharmaceutical and Nano Sciences Journal homepage:
Research Article CODEN: IJRPJK ISSN: 2319 9563 International Journal of Research in Pharmaceutical and Nano Sciences Journal homepage: www.ijrpns.com COMPARARISSION OF SOLUBILITY IMPROVEMENT OF CEFIXIME
More informationE55A GELATIN, GELLING GRADE Gelatina
00-0PDG.pdf 0 0 0 0 EA GELATIN, GELLING GRADE Gelatina DEFINITION Purified protein obtained from collagen of animals (including fish and poultry) by partial alkaline and/or acid hydrolysis, by enzymatic
More informationPreparation and Evaluation of Ethylene Vinyl Acetate Copolymer Coated Microcapsules of Glipizide for Controlled Release
Asian Journal of Chemistry Vol. 21, No. 8 (2009), 5838-5842 Preparation and Evaluation of Ethylene Vinyl Acetate Copolymer Coated Microcapsules of Glipizide for Controlled Release K.P.R. CHOWDARY* and
More informationMethod Development and Validation of Emtricitabine in Bulk by UV Spectroscopy
Human Journals Research Article February 2019 Vol.:14, Issue:3 All rights are reserved by Gandi Anusha et al. Method Development and Validation of Emtricitabine in Bulk by UV Spectroscopy Keywords: Emtricitabine,
More informationSimultaneous estimation of Metformin HCl and Sitagliptin in drug substance and drug products by RP-HPLC method
International Journal of Chemical and Pharmaceutical Sciences 2017, Mar., Vol. 8 (1) ISSN: 0976-9390 IJCPS Simultaneous estimation of Metformin HCl and Sitagliptin in drug substance and drug products by
More information