World Journal of Pharmaceutical Research SJIF Impact Factor 5.990

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1 SJIF Impact Factor Volume 4, Issue 9, Research Article ISSN FORMULATION AND EVALUATION OF LIPOSOMAL GEL OF LORNOXICAM Himanshi Swami 1*, Ajay Bilandi 2, Mahesh Kumar Kataria 3, Kamaljot Kaur 4 1 Research Scholar, M. Pharmacy IV Semester (Pharmaceutics), Seth G.L. Bihani S.D. College of Technical Education, Sri Ganganagar. 2 Assistant Professor, Seth G.L. Bihani S.D. College of Technical education, Sri Ganganagar. 3 Professor and Head of Department (Pharmaceutics), Seth G.L. Bihani S.D. College of Technical Education, Sri Ganganagar. 4 Lecturer, Seth G.L. Bihani S.D. College of Technical education, Sri Ganganagar. Article Received on 19 July 2015, Revised on 11 Aug 2015, Accepted on 02 Sep 2015 *Correspondence for Author Himanshi Swami Research Scholar, M. Pharmacy IV Semester (Pharmaceutics), Seth G.L. Bihani S.D. College of Technical Education, Sri Ganganagar. ABSTRACT Lornoxicam is a potent oxicam class of non steroidal antiinflammatory agent (NSAIDS), prescribed for mild to moderate pain and inflammation. The main factor that limits use of NSAIDs is concern over the development of gastrointestinal (GI) side effects. NSAIDs may cause GI tract mucosal injury (e.g. Erosion, ulcers) and GI complications (e.g. bleeding, perforation, obstruction) by conventional dosage form that are administered by oral route. Topical dosage forms provide relatively consistent drug levels for prolonged periods and avoid gastric irritation, as well as the other typical side effects of oral NSAID administration. In this research work liposomal gel of lornoxicam was developed for topical application. Lornoxicam liposomes were fabricated by thin film hydration technique. Bilayer composition of liposomal vesicles was optimized. Preformulation studies (organoleptic studies, melting point, partition coefficient, absorption maxima, FTIR study) were performed for identification of drug. Prepared liposomes of lornoxicam were incorporated into a gel using Carbopol 941. Rheological and texture properties of prepared gel formulation showed suitability of the gel for topical application. The developed formulation was evaluated for drug entrapment efficiency, ph measurement, in vitro drug release, drug content, and skin irritation studies etc. Formulation F2 (lecithin: drug: cholesterol 100:10:10) was selected as optimized formulation and all the parameters viz. percentage yield, entrapment efficiency, Vol 4, Issue 9,

2 spreadability, viscosity, drug release were found bettter. The results of all tests were found to be satisfactory within the prescribed limits. The formulations showed higher R 2 values for Higuchi Equation plots indicating that drug release followed Higuchi Equation kinetics. KEYWORDS: Lornoxicam, thin film hydration technique, liposomal gel, drug entrapment efficiency INTRODUCTION Oral administration is the most convenient and preferred means of any drug delivery to the systemic circulation. Oral administration of most of the drugs in conventional dosage forms has short-term limitations due to their inability to restrain and localize at gastro-intestinal tract. The drug has to be delivered for a prolonged period of time and many medicines have to be taken simultaneously in case of chronic patients, frequent administration is necessary when those have shorter half-life. Skin has been considered as an alternative route for local and systemic treatment. Topical dosage forms provide relatively consistent drug levels for prolonged periods and avoid gastric irritation, as well as the other typical side effects of oral NSAID administration. NSAIDS have been widely used for decades to relieve pain, inflammation, and fever. Topical application of liposome vesicles has many advantages over the conventional dosage forms. It has been suggested that the formulated liposomes may be applied to the skin as gel. [1] The results of some studies have been indicated that liposomes can increase the deposition of drugs within the skin at the site of action and reduce its absorption into blood. [2,3] Drugs encapsulated in liposomes can be transported without rapid degradation and minimum side effects to the recipients. [4] Lornoxicam is, (3E)-6-chloro-3-[hydroxyl {pyridine-2-ylamino} methylene]-2-methyl-2,3- dihydro-4hthieno[2,3-e][1,2]thiazin-4-one 1,1-dioxide has molecular weight and chemical formula is C 13 H 10 ClN 3 O 4 S 2. [5] as shown in figure1. Lornoxicam, an oxicam class of nonsteroidal anti-inflammatory drug, inhibits cyclooxygenase enzyme and thereby interferes with prostaglandins synthesis. This leads to desensitization of peripheral nociceptors which further reduces inflammation, [6,7] It is prescribed for mild to moderate pain and inflammation in osteoarthritis and rheumatoid arthritis, ankylosing spondylitis and various rheumatic conditions such as tendinitis, bursitis, sciatic, back pain and gouty arthritis. [8] The main factor that limits use of NSAIDs is concern over the development of GI side effects viz. mucosal Vol 4, Issue 9,

3 injury (e.g. Erosion, ulcers) and GI complications (e.g. bleeding, perforation, obstruction) by conventional dosage form that are administered by oral route. The adult dosage of Lornoxicam for pain relief is 8-16mg daily and maximum of 24mg/day. The daily dosage for Osteoarthritis is 12 mg daily in 2-3 divided doses, up to 16 mg daily. Lornoxicam is practically insoluble in water. [9,10] Thus the liposomal gel of lornoxicam may be prepared with carbopol 941, well proven and acceptable gelling agent having least limitation. Figure 1 Structure of Lornoxicam MATERIAL Lornoxicam and carbopol 941 was kindly provided by Ananta Medicare Ltd. Sri- Ganganagar, cholesterol from central drug house (P) ltd. New Delhi and soya lecithin from Vinubhai agencies Pvt. Ltd., Mumbai. All other chemicals and reagents used were laboratory reagent grade. METHODS Preformulation Studies of drug and excipients Preformulation studies are the first step in the rational development of dosage forms of a drug substance. It can be defined as an investigation of physical and chemical properties of a drug substance alone and when combined with excipients. The overall objective of preformulation testing is to generate information useful to the formulator in developing stable and bioavailable dosage forms. Organoleptic properties The organoleptic studies like general appearance like nature, color, odor, etc. were performed by visual observation. The sample of drug was observed for colour, state. Vol 4, Issue 9,

4 Melting point For determination of melting point USP method was followed. Small quantity of drug was placed into a sealed capillary tube. The tube was placed in melting point apparatus. The temperature in the apparatus was gradually increased and the observation of temperature was noted at which drug started to melt and the temperature when the entire drug gets melted. Drug identification By absorption spectrum method Drug solution of 100µg/ml was prepared using phosphate buffer ph 7.4 and UV scan was taken to determine λmax. By infra-red spectrum method Accurately weighed 10 mg of lornoxicam was taken in vial and FTIR spectra were taken for the fresh sample and sample kept at 50 o C for 15 days. Drug excipients compatibility study Drug excipients compatibility study by FTIR Before formulating a dosage form it is very necessary to confirm that drug is not interacting with the polymer under certain experimental conditions. Interaction among drug and polymer may affect the efficacy of final dosage form. Drug and excipients were accurately weighed and mixed and the resulting mixtures were scaled in screw glass vials and kept at a 50 C for 15 days [11]. The FTIR spectra of all the samples were taken for fresh samples and samples stored at 50 C for 15 days. Table 1: Drug Excipients Compatibility Studies S. No. API and Excipients Drug : Excipient Ratio Quantity per vial (mg) Initial No. of Vials At 50 0 C for 15 days 1 Lornoxicam Carbopol Cholesterol Soya lecithin Lornoxicam + carbopol 941 Lornoxicam + soya lecithin Lornoxicam+ cholesterol : : Vol 4, Issue 9,

5 Partition coefficient studies Partition coefficient (oil/water) is a measure of a drug s lipophilicity and an indication of distributed between the organic and aqueous phases at equilibrium. Partition coefficient provides a means of characterizing the lipophilic/ hydrophilic nature of a drug. Partition coefficient of lornoxicam was determined at 37±0.50 C by taking 25ml octanol and 25ml of phosphate buffer. After shaking the system remained undisturbed for half an hour. About 10mg of a drug was added to this solution and the above formed mixture was left undisturbed for about 24hrs. Two layers were separate through separating funnel and the amount of lornoxicam solubilized, was determined by measuring the absorbance at 376.6nm against reagent blank through double beam UV/Vis spectrophotometer in both the solution. Partition coefficient was determined as a ratio of concentration of drug in octanol to the concentration of drug in phosphate buffer and the value were reported as logp. [12] Development of standard calibration curve Accurately weighed 10 mg of drug, dissolved in sufficient volume of phosphate buffer ph 7.4 and then made up volume up to 100 ml with phosphate buffer ph 7.4 and then working solutions of different concentrations (2, 4, 6, 8, 10 μg/ml) were prepared. The absorbance was obtained at λmax 376.6nm and calibration curve was plotted between concentration and absorbance. FORMULATION LIPOSOMAL GEL OF LORNOXICAM Formulation of Liposomes Liposomes were prepared by thin film method. Soya lecithin, cholesterol, vitamin E (as antioxidant) and 10 mg lornoxicam were dissolved in 5ml chloroform. The quantities of lecithin and cholesterol were changed to enhance loading drug in liposomes. Then the mixture was evaporated in a rotary evaporator at 150 rpm with temperature below the boiling point of chloroform (62 0 C) until the thin film formed in round bottomed flask (approximately min). Then it was hydrated with phosphate buffer saline for 30min. Different ratio of all ingredients are given below in table 2. [13,14] Table 2: Formulation with Different Ratio Formulation No. Compositions ratio (mg) (lecithin: drug: cholesterol) F1 100:10:5 F2 100:10:10 F3 100:10:20 F4 100:10:40 F5 100:10:60 Vol 4, Issue 9,

6 Preparation of Small Unilamellar vesicle liposome The liposomes prepared are Multilamellar vesicle (MLV). Small Unilamellar vesicle (SUV) liposomes were obtained by sonication of MLV liposome in an ultrasonic bath for 30min at room temperature, as shown in figure 2. Figure 2: Preparation liposomes by rotary evaporator Preparation of liposomal gel Carbopol 941 (aqueous 1%) was added slowly to a phosphate buffer saline solution (ph 7.4), under constant stirring by a paddle stirrer. For gel preservation, methyl paraben (0.2%) was added. Then teriethanolamine was added for achieving neutral ph and clearing of the gels. After addition of the full amount of solid material, the gels were allowed to swell under moderate stirring. [15] Evaluation tests for Small Unilamellar vesicle (SUV) liposomes Determination of lornoxicam entrapment in liposomes The liposomal suspension was centrifuged at 3000 rpm for 3-4hrs. The supernatant was removed and the liposomes were disrupted with ethanol 70% and the quantity of drug was measured using a spectrophotometer at nm. Entrapment efficiency = 100 Percentage Practical Yield The prepared liposomes were collected and weighed. The measured weight was divided by total weight of all the excipients and drug. The % practical yield was calculated using following formula: % Practical Yield = Total liposomes weight/ Total theoretical weight. Vol 4, Issue 9,

7 Drug content 1 g of the prepared gel was mixed with 100ml of suitable solvent. Aliquots of different concentration were prepared by suitable dilutions after filtering the stock solution and absorbance was measured. Drug content was calculated using the equation, which was obtained by linear regression analysis of calibration curve. In-vitro drug release study from liposomes Studies of the drug release/diffusion from liposomal system are directed toward the approaches that are relevant to the in vivo condition. In vitro diffusion studies were carried out using Franz diffusion cell, apparatus with a diameter of 25 mm and a diffusional area of 4.90 cm 2. Egg membrane was sandwiched between the lower cell reservoir and the glass cell top containing the sample and secured in place with a pinch clamp. The receiving compartment has volume of 22ml. The system was maintained at 37±0.5 C by magnetic heater, resulting in a membrane-surface temperature of 32 C. A Teflon coated magnetic bar continuously stirred the receiving medium to avoid diffusion layer effects. A sample was placed evenly on the surface of the membrane in the donor compartment. 2ml of receptor fluid were withdrawn from the receiving compartment at 5, 10, 15, 30, 45, 60mins and replaced with 2ml of fresh phosphate buffer saline solution. Samples were assayed spectrophotometrically for drug content at 376.6nm. Optimization of formulation Formulation that shows the best results for above evaluation tests had been finalized as optimized formulation. Evaluation tests of optimized formulation Measurement of ph The exact amount of Lornoxicam gels was weighed in a 25ml volumetric flask and then volume was made up with double distilled water to 25 ml. The ph of the gel was measured using a digital ph meter by getting it in contact to equilibrate it for 1 min. ph evaluation was carried out in triplicate for all formulations. [16] Viscosity study The viscosity measurements of the gels were determined at 25 C using a Brookfield Viscometer. All viscosity measurements were performed in triplicate. [16] Vol 4, Issue 9,

8 Homogeneity After the gels have been set in the container, all developed gels were tested for homogeneity by visual inspection. They were tested for their appearance and presence of any aggregates. [17] Spreadability A sample of 0.5g of each formula was pressed between two slides (divided into squares of 5mm sides) and left for about 5 min where no more spreading was expected. Diameters of spreaded circles were measured and were taken as comparative values for spreadability. The results obtained are average of three determinations. Skin irritation study The gel formulation that shows the highest release was selected for testing skin irritation. It was carried out on five human volunteers. A half gram of gel F 2 was applied in the hand of each volunteer for 24 hours. After removal of gel, the resultant skin effects were examined for the sign of erythema or itching. The effects were classified into 5 scores depending on the degree of erythema as follows: 0 (no erythema), 1 (slight erythema-light pink), 2 (moderate erythema-dark pink), 3 (moderate to severe erythema-light red), and 4 (severe erythemaextreme redness). Release kinetics Release kinetics models, which described the overall release of drug from the dosage forms. Because qualitative and quantitative changes in formulation may alter drug release and in vivo performance, developing tools that facilitate product development by reducing the necessity of bio studies is always desirable. In this regard, the use of in-vitro drug dissolution data to predict in vivo bio-performance can be considered as rational development of controlled release formulations. Data obtained from the in vitro release studies were fitted to various model dependent kinetic equations such as zero order, first order, higuchi model, and korsmeyer- peppas model. Zero- order model Q t = Q 0 + Kt First order model: Log C= log C 0 - Kt/2.303 Higuchi model: Vol 4, Issue 9,

9 Q= K H *t 1/2 Korsmeyer- peppas model: Q/Q 0 = Kt n Where, K 0 to K H were release rate constant, Q/Q 0 was fraction of drug released at time t, K was a constant and n was diffusion constant that indicates general operating release mechanism. For fickian (diffusion controlled) n 0.5; for non-fickian (anomalous) release, n value is in between 0.5 to 1.0; for zero order release, n=1.o; for super case transport II, n> Based on the slop and the R 2 value obtained from the above models the mechanism of drug release was decided. RESULTS AND DISCUSSION Preformulation studies Organoleptic properties Table 3: Description of drug Melting point S. No. Properties Inference 1. Colour Yellow Colored 2. State Powder 3. Odour Odorless Observed melting point was C. It complies with standard melting point range C as shown in table 4. Table 4: Measurement of melting point Drug Lornoxicam Melting point C Drug identification By absorption spectrum method The absorption spectrum of pure drug was scanned between nm with 25µg/ml concentration prepared in phosphate buffer ph 7.4. The absorption spectrum of resulting solution, when observed between 210 and 400nm, exhibits maxima about 376.6nm these peaks are similar to that given in standards. Vol 4, Issue 9,

10 Transmittance [%] Transmittance [%] Himanshi et al. Figure 3: Absorption Spectra of Lornoxicam By infra-red spectrum method Drug and polymers identified by infra-red spectrum. The IR spectrum given below shown that the peaks of the drug Wavenumber cm-1 Figure 4: FTIR spectrum of lornoxicam (fresh sample) D:\backup\BRUKER\ \ Instrument type and / or accessory 16/02/2015 Page 1/ Wavenumber cm-1 Figure 5: FTIR spectrum of lornoxicam (after 15 days at 50 C) D:\backup\BRUKER\ \ Instrument type and / or accessory 18/02/2015 Page 1/1 Vol 4, Issue 9,

11 Transmittance [%] Himanshi et al. The Infrared spectra of lornoxicam were recorded between 600to3500cm-1 on FTIR. From the FTIR studies at and are the characteristics peaks of lornoxicam. Peaks obtained in spectrum of pure drug (fresh & after 15 days) were similar to that given in standard. Drug- excipients compatibility study Drug and excipients were accurately weighed and mixed and the resulting mixtures were scaled in screw glass vials and kept at a 50 C for 15 days the possible interaction between the drug and excipients were studied by Infra-red spectroscopy. Below spectrum shows the peaks of pure drug sample and polymers as compare to standard drug sample i.e. no chemical reaction occurs between polymers and drug sample Wavenumber cm-1 Figure 6: FTIR spectra carbopol 941(Fresh) D:\backup\BRUKER\ \ Instrument type and / or accessory 16/02/2015 Page 1/1 Figure 7: FTIR Carbopol 941 (after 15 days at 50 C) Vol 4, Issue 9,

12 Transmittance [%] Transmittance [%] Himanshi et al Wavenumber cm-1 Figure 8: FTIR Spectrum Cholesterol (Fresh) D:\backup\BRUKER\ \ Instrument type and / or accessory 18/02/2015 Page 1/1 Figure 9: FTIR Spectrum Cholesterol (after 15 days) Wavenumber cm-1 Figure 10: FTIR Spectrum Soya lecithin (fresh) D:\backup\BRUKER\ \ Instrument type and / or accessory 18/02/2015 Page 1/1 Vol 4, Issue 9,

13 Transmittance [%] Himanshi et al. Figure 11: FTIR Spectrum Soya lecithin (after 15 days at 50 C) Wavenumber cm-1 Figure 12: FTIR Spectrum of lornoxicam with carbopol 941 (Fresh) D:\backup\BRUKER\ \ Instrument type and / or accessory 16/02/2015 Page 1/1 Figure 13: FTIR Spectrum of lornoxicam with carbopol 941 (after 15 days at 50 C) Vol 4, Issue 9,

14 Transmittance [%] Transmittance [%] Himanshi et al Wavenumber cm Figure 14: FTIR Spectrum of lornoxicam with cholesterol (fresh) D:\backup\BRUKER\ \ Instrument type and / or accessory 16/02/2015 Page 1/1 Figure 15: FTIR Spectrum of lornoxicam with cholesterol (after 15 days at 50 C) Wavenumber cm Figure 16: FTIR Spectrum of lornoxicam with soya lecithin (fresh) D:\backup\BRUKER\ \ Instrument type and / or accessory 18/02/2015 Page 1/1 Vol 4, Issue 9,

15 Figure 17: FTIR Spectrum of lornoxicam with soya lecithin (after 15days at 50ºC) FT-IR study showed that there was no major change in position of peaks obtained in alone and mixture of excipients and drug, which shows that there was no interaction between drug and polymers. (excipients) Partition coefficient studies Partition coefficient, the log p of Lornoxicam is 1.7 and this value is less than 2.5 which means expected improvement in Lornoxicam absorption. Yano et al. stated that the optimum log p value for NSAIDs is 2.5; so the absorption rate would increase in drugs with log p value less than 2.5. Development of Calibration Curve The calibration curve for lornoxicam was prepared in phosphate buffer solution ph7.4 and phosphate buffer saline ph7.4. Table 5: Standard calibration curve in phosphate buffer ph7.4 at λ max 376.6nm Concentration(µg/ml) Absorbance Vol 4, Issue 9,

16 Figure 18: Standard calibration curve in phosphate buffer ph7.4 at λ max nm Table 6: Standard calibration curve in phosphate buffer saline solution ph 7.4 at λ max nm Concentration(µg/ml) Absorbance Figure 19: Standard calibration curve in phosphate buffer saline solution ph 7.4 at λ max nm Formulation of Liposomes Liposomes were prepared by using different concentration ratio of lecithin, drug, and cholesterol. Preparation of Small Unilamellar vesicle liposome and liposomal gel SUV were prepared by using sonicator and gels of drug loaded liposomes were prepared using carbopol 941(1%). Vol 4, Issue 9,

17 Evaluation Test Evaluation tests for Small Unilamellar vesicle liposome Small Unilamellar vesicles were evaluated for entrapment efficiency and percentage practical yield. Determination of lornoxicam entrapment in liposomes The liposomal suspension was centrifuged at 3000 rpm for 3-4hrs. The supernatant was removed and the liposomes were disrupted with ethanol 70% and the quantity of drug was measured using a spectrophotometer at 376.6nm. Table 7: Drug entrapment efficiency of lornoxicam Formulation.No Compositions ratio in mg Entrapment LECITHINE DRUG CHOLESTEROL efficiency (%) F F F F F Figure 19: drug entrapment efficiency of lornoxicam Results of drug entrapment efficiency are shown in table (7). The drug entrapment efficiency of the formulated (F 2 ) was estimated and the results were in the range of 34 to 79 %. The drug entrapment determination also showed that the drug was uniformly distributed throughout the preparation. Percentage practical yield Percentage practical yield of different formulation was determined by weighing. The percentage yield of different formulation was in range % as shown in table (8). The maximum percentage yield was found in F 2. Vol 4, Issue 9,

18 Table 8: Percentage yield of liposome Formulation Batch Initial Weight of Ingredients (mg) Theoretical Yield (mg) Yield of Formulation (mg) % Yield F F F F F Drug content Figure 20: Percentage yield of liposome Prepared liposomal gels of lornoxicam were evaluated for drug content. The drug content of different formulation was in range % as shown in table (9). The drug content was found in F 2 (table 9) Table 9: Drug Content Formulation Batch Total drug in mg Drug Content Drug content in % F F F F F Vol 4, Issue 9,

19 Figure 21: Drug Content In-vitro drug release study Cumulative % release of different prepared formulations was calculated by using franz diffusion cell as shown in table Cumulative % release formulation F1: Table 10: Cumulative % release formulation F1 Time Absorbance Concentration Concentration20ml Cumulative % Cumulative % release formulation F2 Table 11: Cumulative % release formulation F2 Time Absorbance Concentration Concentration 20ml Cumulative % Cumulative % release formulation F3 Table 12: Cumulative % release formulation F3 Time Absorbance Concentration Concentration 20ml Cumulative % Vol 4, Issue 9,

20 Cumulative % release formulation F4 Table 13: Cumulative % release formulation F4 Time Absorbance Concentration Concentration 20ml Cumulative % Cumulative % release formulation F5 Table 14: Cumulative % release formulation F5 Time Absorbance Concentration Concentration 20ml Cumulative % Cumulative % Release at final formulation Table 15: Cumulative % Release at final formulation Time F1 F2 F3 F4 F5 0min min min min min min min In vitro drug release studies of all the formulations of liposomal were carried out in phosphate buffer saline ph 7.4 solution. It was observed that ratio of lecithin, drug, cholesterol, influences the drug release pattern. Formulations with different ratio (F 2, and F 3 ) showed high release of drug when compared to formulations with other ratio (F 1, F 4, and F 5 ). Vol 4, Issue 9,

21 The plot of cumulative percentage drug release V/s time (hr.) for all formulations was plotted and depicted in Figure (22) respectively. Figure 22: Comparative Dissolution Profile Data of all Formulation Figure 23: Comparative Dissolution Profile Data of all Formulations Optimization of formulation As per as the percentage yield, drug content and dissolution studies are concerned, it indicated that F2 formulation gives best percentage practical yield, and drug content shows best dissolution release. By the result observation, it can conclude that F2 formulation should be a better candidate for liposomal gel. So evaluation test of F2 formulation was performed. Evaluation of the selected formulation Measurement of ph The ph values of the Lornoxicam gel F2 was found to be in the range from7.2 to 7.8, which probably would not produce skin irritation. Hence, the prepared Lornoxicam gels are suitable for dermatological purpose. Vol 4, Issue 9,

22 Table 16: Measurement of ph Viscosity study S.NO. ph determination Average± S.D ± Viscosity plays an important role in controlling the drug permeation. Generally viscosity of gel formulations reflects its consistency. For topical analgesic formulations, the consistency of the samples is specially an important feature, due to the fact that it must be applied to the skin in thin layers. For this reason, it is preferable to formulate non-newtonian flow system because of its low resistance to flow when applied under high shear conditions. In this study, gel formulations showed non-newtonian flow (shear thinning). Homogeneity The prepared gel F2 inspected visually for their color. The developed preparation was clear and transparent. The developed gel F 2 showed good homogeneity with absence of lumps. Spreadability The spreadability is very much important as show the behaviour of gel comes out from the tube. The values of spreadability shown in table (17) indicate that polymers used gave gels spread by small amount of shear. The diameters of the spreaded circles ranged from2.4 gm. cm 2 to 3.5 gm. cm 2. Table 17: Spreadability of the Liposomal Gel spreadability determination S.NO. in gm.cm Average ± S.D. 3± The prepared gels should have good Spreadability to meet ideal quality in the field of topical application. It is reported that the therapeutic efficiency of the gels also depends upon its spreading. The Spreadability has an important character in patient compliance and helps in uniform application of the gel to the skin. If the gel has less time spread, it is considered a good gel with high Spreadability value. The Spreadability of prepared gels was of high values. Vol 4, Issue 9,

23 Skin irritation study The gel formulation (F2) was selected for testing skin irritation. It was carried out on five human volunteers after removal of gel, the resultant skin effects were examined for the sign of erythema as shown in table 18. Table 18: Skin irritation study RELEASE KINETICS Volunteers No. Erythema 1 No 2 No 3 No 4 No 5 No The in vitro release data obtained from Formulation F2 was fitted to kinetic models shown in Table In case of zero order the graph was plotted in cumulative percent of drug released versus time and in first order release kinetics ((Log C= log C 0 - Kt/2.303) the graph was plotted in log cumulative percent of drug remaining versus time. For Higuchi model kinetics (Q= K H t 1/2 ) the graph was plotted in cumulative percent of drug released versus square root of time, and for Korsmeyer-Peppas model (Q/Q 0 = Kt n ) the graph was plotted in log cumulative percent of drug released versus log time. The release of lornoxicam from the liposomal gel was Korsmeyer-peppas model diffusion controlled as indicated by highest R 2 values in Higuchi model. Table 19: Release kinetics of liposomal gel of lornoxicam from formulation F2 Time Square root of time log time %CDR log % CDR log % CDR remaining 0 min min min min min min min Zero order Equation Table 20: Zero Order Equation TIME %CDR 0 min. 0 5min min Vol 4, Issue 9,

24 15 min min min min First order Equation Table 21: First order Equation Figure 24: Zero Order Equation TIME LOG %CDR REMAINING 0 0 5min min min min min min Higuchi Equation Table 22: Higuchi Equation Figure 25: First orders Equation SQUARE ROOT OF TIME % CDR Vol 4, Issue 9,

25 Korsmeyer Peppas equation Table 23: Korsmeyer Peppas equation Figure 26: Higuchi Equation log time log % CDR Figure 27: Korsmeyer Peppas equation The formulation showed higher R 2 values (R 2 =0.972) for Higuchi plots indicating that drug release followed Higuchi model. CONCLUSION Various formulations (F1-F5) were developed by using suitable polymer (carbopol 941). Preformulation study for absorption maxima, result complies with the standards. Vol 4, Issue 9,

26 Preformulation study for drug- excipients compatibility study by FTIR showed no interaction between drug and selected excipients. Entrapment efficiency % was optimized after studying the effect of various ratios and formulation process. Maximum entrapment efficiency was 78.70% with formulation F2. The maximum percentage yield from optimized batch i.e. F2 was found to be 91.29%. Maximum drug content from optimized batch i.e. F2 was found to be 91.32%. The percentage cumulative drug release from optimized batch i.e. F2 was found to be after one hour of diffusion studies. Viscosity study, skin irritation study, spreadability of gel from F2 formulation was same as pr standards. In skin irritation studies, no irritation occurs after application of gel preparation. So it is suitable for topical application. The release rate of drug best fitted to Higuchhi model. ACKNOWLEDGEMENT I offer my adoration to who created me, gave me the strength and courage to complete my thesis and given me the opportunity to thanks all those people through whom this Grace was delivered to me. I take it as a privilege to sincerely express my deep sense of gratitude and thank my guide, Dr. Mahesh Kumar Kataria, Professor, Head of department of pharmaceutics, Seth G. L. Bihani S. D. College of Technical Education Sri Ganganagar (Raj.) I express my heartfelt thanks to Mr. Ajay Bilandi, Assistant Professor for providing inspiring support, valuable suggestions and guidance. I am blessed indeed to have such caring and loving parents, my mother Smt. Usha Swami, my father Mr. Ram Kumar Swami. REFERENCES 1. Glavas-Dodov M., Simonoska M., K. Goracinova. Formulation and characterization of topical liposome gel bearing lidocaine HCl., Maced. J. Chem. Chem. Eng., 2005; 24: Maghaby G, Barry BW, Willians AC. Liposomes and skin: from drug delivery to model membranes. European J Pharmaceutical Sciences., 2008; 34: Egbaria K, Weiner N. Liposomes as a topical drug delivery system. Advanced drug delivery reviews., 1990; 5: Goyal P, Goyal K, Kumar SGV, Singh A, Katare OP, Mishra DN. Liposomal drug delivery systems-clinical applications, Acta Pharm., 2005; 55: Hitzenberger G, Welte SR, Takacs F, Rosenow D. Pharmacokinetics of lornoxicam in man. Postgrad Med J., 1990; 66(4): S Vol 4, Issue 9,

27 6. Zhang Y, Zhong D, Si D, Guo Y, Chen X, Zhou H. Lornoxicam pharmacokinetics in relation to cytochrome P450 2C9 genotype. Br J Clin Pharmacol., 1990; 59(1): Norholt SE, Sindet-Pedersen S, Larsen U, Bang U, Ingerslev J, Nielsen O, et al. Pain control after dental surgery: a double-blind, randomised trial of lornoxicam versus morphine. Pain., 1990; 67: Staunstrup H, Ovesen J, Larsen UT, Elbaek K, Larsen U, Kroner K.Efficacy and tolerability of lornoxicam versus tramadol in postoperative pain. J Clin Pharmacol., 1990; 39: Skjodt NM, Davies NM. Clinical pharmacokinetics of lornoxicam: a short half-life oxicam. Clinical Pharmacokinetics., 1990; 34(6): HamzaYES, AburahmaMH. Innovation of novel sustained release compression-coated tablets for lornoxicam: formulation and in vitro investigations. Drug Dev Ind Pharm., 1990; 36(3): Hartauer KJ, Guillory JK. A Comparison of diffuse Reflectance Ft-IR Spectroscopy and DSC in the Characterization of a Drug-Excipient Interaction. Drug Dev Ind Pharm., 1990; 17(4): Y. Krishna Reddy, D. Maheswara Reddy, M. Asok Kumar. Transdermal Drug Delivery System: A Review. Indian Journal of Research in Pharmacy and Biotechnology., 1990; Agarwal R, Katare OP. Preparation and In Vitro Evaluation of Miconazole Nitrate Loaded Topical Liposomes. Pharmaceutical Technology., 1990; Chetanachan P, Akarachalanon P, Worawirunwong D, Dararutana P, Bangtrakulonoth A, Bunjop Kongmuang S. Ultrastructural characterization of liposome using transmission electron microscope. Advanced Materials Research., 1990; Eskandar Moghimipour, Mohsen Tafaghodi, Ali Balouchi, Somayeh Handali Formulation and in vitro Evaluation of Topical Liposomal Gel of Triamcinolone Acetonide. RJPBCS., 2013; 4(1); Saleh A. Al-Suwayeh, Ehab I. Taha, Fahad M. Al-Qahtani, Mahrous O. Ahmed, and Mohamed M. Badran. Evaluation of Skin Permeation and Analgesic Activity Effects of Carbopol Lornoxicam Topical Gels Containing Penetration Enhancer. Hindawi Publishing Corporation Scientific World Journal., 1990; Baviskar, Dheeraj T et al. In Vitro and In Vivo Evaluation of Diclofenac Sodium Gel Prepared with Cellulose Ether and Carbopol 934P Tropical Journal of Pharmaceutical Research., 1990; 12(4): Vol 4, Issue 9,