Content Uniformity of Direct Compression tablets
|
|
- Silas Bruce
- 5 years ago
- Views:
Transcription
1 Content Uniformity of Direct Compression tablets
2
3 Contents 1 Summary 4 2 Introduction 4 3 The role of drug particle size 4 4 The role of mixing strategy 5 5 The role of excipients 5 6 Laboratory data 6 7 Conclusions 11 8 References 11 Content Uniformity of Direct Compression tablets 3
4 1 Summary Achieving good tablet content uniformity requires drug particle size to be controlled such that there are enough particles in a single dose to achieve adequate distribution. It is essential to effectively deagglomerate the drug. Both the mixing scheme and the selection of fillerbinder contribute to deagglomeration. The mixing scheme should include a step specifically to reduce agglomerates in a drug excipient premix to a sub-critical level, and free flowing excipients such as SuperTab 30GR or SuperTab 11SD can aid in the dispersal of agglomerates. 2 Introduction Direct compression is the simplest way of making tablets, requiring only blending and tableting operations for low and medium dose APIs where the tableting properties are primarily conferred by excipients. In order to make satisfactory tablets by direct compression, especially when the API dose is low, it is necessary to understand the factors that contribute to achieving acceptable drug content uniformity. These may be summarised as drug particle size, mixing strategy and selection of key excipients (filler-binders). This guide discusses these three factors, and is illustrated with data from DFE Pharma s laboratory. 3 The role of drug particle size This factor is not confined to direct compression. Any dosage form containing particles of a drug must contain enough particles to enable them to be distributed evenly between individual dosage units. Pharmacopoeial requirements for content uniformity are based on both the standard deviation of the data, calculated as an acceptance value (AV) and on the range of the data. The acceptance value must not exceed 15.0 at level 1 (analysis of 10 units) or 25.0 at level 2 (analysis of 30 units). The acceptance value is calculated as = +..equation 1 where M = X (if 98.5 < X < 102.5) or M = 98.5 (if X < 98.5) or M = (if X > 102.5), X is the sample mean assay value, k is 2.4 (level 1) or 2.0 (level 2) and s is the sample standard deviation. The AV corresponds to an RSD of 6.25% at level 1 or an RSD of 7.5% at level 2 when X=100. The range of the data must be within % of the label strength at level 1 or within % of the label strength at level 2. It is possible to relate the potential RSD that is achievable for an API to its dose and its particle size distribution. The general approach is based on consideration of the Poisson distribution which has the property that the mean is equal to the variance. Thus it is possible to express the RSD of a Poisson distribution as = 100 equation 2 where n is the average number of drug particles in a single unit. The number of drug particles is related to the dose (G) and the particle diameter (d), and the RSD can be written in terms of these parameters as =100 equation 3 where ρ is the true density of the API. The diameter to be taken is the volume-weighted, volume-number mean diameter (Egermann 1982). Development of this approach (Rohrs 2005) leads to calculation of the required geometric median diameter (d g) to achieve a given RSD. = 10 {.[. ]}.. equation 4 where σ g is the geometric standard deviation of the API particle size distribution. 4 Content Uniformity of Direct Compression tablets
5 To have a 99% chance of passing content uniformity criteria at level 1 requires an RSD of 3.84 (Rohrs 2005; based on USP28 criteria). Using this value in equation 4 and assuming the API has true density of 1.5 g.cm -3 results in the values shown in table 1. For example, a 1 mg dose of an API requires a d 50 of about 35 µm or less if the ratio d 90/d 50 is about 3.2. Measure of spread Dose (mg) of API distribution σ g d 90/d Table 1: Maximum particle median diameter (d 50) required to give a 99% chance of passing USP content uniformity requirements at level 1. 4 The role of mixing strategy Many APIs are finely milled powders and are consequently cohesive with a tendency to agglomerate. An appropriate mixing strategy includes a step to disperse these agglomerates to a sub-critical level (a level which is unlikely to threaten the content uniformity requirements). Importantly this de-agglomeration step should not be performed on the API itself, because of the tendency to agglomerate again (Egermann 1979), but it should be performed on a premix of the API (approximately 10%) and an excipient (approximately 90%). The overall processing scheme is therefore Premixing De-agglomeration Final mixing Lubrication Tableting Deagglomeration may be performed by a variety of unit processes, including sieving, passing a premix through a conical type mill, use of a blender with an intensifier bar or other high shear step. It has been suggested that a critical agglomerate size is such that no single agglomerate exceeds 5% of the total API dose (Egermann 1979). The sieve aperture through which a premix should be passed in order to meet this requirement can be estimated. Table 2 is based on Egermann 1979 with the assumption that the bulk density of the agglomerates is 0.5 g.cm -1. For example a premix of an API with dose of 1 mg needs to passed through an ASTM 35 mesh / 500 µm sieve or finer. For doses below 1 mg of API it may be preferred to make a premix with an excipient finer than direct compression lactose. Dose of API (mg) Maximum agglomerate size (µm) Closest ASTM equivalent sieve 120# 70# 60# 40# 35# 18# 16# ISO equivalent mesh 125 µm 212 µm 250 µm 425 µm 500 µm 1 mm 1.18 mm Table 2: Maximum sieve aperture required to reduce agglomerates to a sub-critical level 5 The role of excipients Selection of appropriate excipients, particularly filler-binders, may affect the content uniformity of tablets. It has been found (Staniforth 1982 and 1987) that a macroporous excipient (one with surface cavities) is beneficial in promoting physical stability of blends of coarse excipients and fine drugs, for a number of reasons. First, there is the opportunity for multiple adhesive contact points between drug and excipient, and also the location of drug particles in surface cavities means that they are less likely to be detached by rolling or abrasive forces during mixing. Content Uniformity of Direct Compression tablets 5
6 Differences in the surface structures of different types of lactose are shown in figure 1 which shows that granulated forms of direct compression lactose possess appear to have the most surface cavities. (a) Granulated Lactose (b) Spray Dried Lactose (c) Anhydrous Lactose Figure 1: Surface structures of various forms of direct compression lactose by SEM Examples of granulated lactose for direct compression include grades of lactose monohydrate (SuperTab 30GR and LactoPress Granulated), and anhydrous lactose (SuperTab 24AN). 6 Laboratory data In the experiments described here, paracetamol was used as a model drug and the filler-binders were SuperTab 11SD, SuperTab 30GR (both direct compression lactose monohydrate), SuperTab 21AN, SuperTab 22AN (both direct compression anhydrous lactose) and Pharmacel 102 (microcrystalline cellulose). The particle size distributions as determined by Sympatec laser diffraction are shown in the table below. Component Particle size distribution (µm) d 10 d 50 d 90 Paracetamol 3, SuperTab 11SD SuperTab 30GR SuperTab 21AN SuperTab 22AN Pharmacel According to table 1, the paracetamol (d 50 = 18 µm, d 90 / d 50 = 4.0) is suitable for doses of approximately 0.5 mg and higher. Tablet formulations contained 2% paracetamol (equivalent to 5 mg), 97.5% of the filler binder and 0.5% magnesium stearate. Blends (4 kg scale) were prepared according to one of the mixing schemes described below and tableted at 250mg using a Kilian RTE-15 AM rotary press with 9mm tooling (lactose tablets) or 10 mm tooling (Pharmacel 102 tablets). Tablet samples were taken throughout the tablet run (approximately 30 minutes) and at each sampling time 10 tablets were tested for weight uniformity and content uniformity. Paracetamol was analysed by ultraviolet spectroscopy in water at 243nm, and the assay was determined to have RSD of 1.3%. scheme A (no deagglomeration step): The paracetamol and the filler-binder were blended in a cube mixer for 10 minutes and then the magnesium stearate was added and blended for a further 5 minutes. scheme B (including deagglomeration): The paracetamol (80g) was blended with 500 g of the filler-binder in a Turbula mixer at 90 rpm for 5 minutes. This premix was passed through a 500 µm sieve before blending with the remainder of the filler binder in a cube mixer and lubrication. The maximum sieve aperture required for a 5 mg dose of API is 1000 µm according to table 2, and therefore the final blend should not contain any agglomerates of a critical size. 6 Content Uniformity of Direct Compression tablets
7 The weight uniformity of tablets made in the study is given in table 3. Weight uniformity is excellent and will not have a significant contribution to content uniformity variation. scheme A (no sieving step) B (including sieving step) Tableting time (min) SuperTab 11SD SuperTab 30GR SuperTab 21AN SuperTab 22AN Pharmacel (0.4) 251 (0.5) 252 (0.5) 251 (0.4) 248 (0.6) (0.4) 249 (0.3) 249 (0.5) 249 (0.3) 249 (0.9) (0.4) 250 (0.5) 249 (0.7) 250 (0.5) 251 (0.8) (0.5) 250 (0.3) 250 (0.5) 250 (0.5) 251 (0.6) (0.4) 250 (0.3) 250 (0.3) 250 (0.4) 252 (1.1) end 249 (0.4) 250 (0.5) 250 (0.5) 249 (0.5) 250 (0.9) (0.2) 251 (0.5) 252 (0.4) 250 (0.4) 252 (0.5) (0.3) 250 (0.3) 249 (0.5) 249 (0.4) 251 (0.5) (0.2) 250 (0.4) 251 (0.7) 249 (0.3) 252 (0.4) (0.2) 249 (0.3) 250 (0.5) 250 (0.3) 251 (0.3) (0.2) 249 (0.3) 249 (0.6) 250 (0.4) 250 (0.2) end 250 (0.4) 251 (0.4) 249 (0.5) 249 (0.4) 250 (0.4) Table 3: Weight uniformity of tablets Content uniformity results for each of the 5 filler-binders evaluated are shown in the tables below. In the Pass / Fail lines the asterisked Fail * notation means that the sample would fail at level 2 if tested. SuperTab 11SD scheme A scheme B Tableting time (mins) end AV Pass / Fail Pass Pass Pass Fail Pass Fail Range (%) Pass / Fail Pass Pass Pass Fail * Pass Fail AV Range (%) SuperTab 30GR scheme A scheme B Tableting time (mins) end AV Range (%) AV Range (%) Content Uniformity of Direct Compression tablets 7
8 SuperTab 21AN scheme A scheme B Tableting time (mins) end AV Pass / Fail Fail Fail Fail Fail Fail Fail Range (%) Pass / Fail Pass Pass Pass Pass Pass Fail * AV Range (%) SuperTab 22AN scheme A scheme B Tableting time (mins) end AV Pass / Fail Pass Fail Pass Pass Pass Pass Range (%) Pass / Fail Pass Fail * Pass Pass Pass Pass AV Range (%) Pharmacel 102 scheme A scheme B Tableting time (mins) end AV Pass / Fail Fail Fail Fail Fail Fail Fail Range (%) Pass / Fail Fail * Fail * Fail Fail * Fail * Fail * AV Range (%) The data for the content uniformity of the tablets are plotted below. The data for mixing scheme A (without sieving) are plotted in grey, and the data for mixing scheme B (with sieving) are plotted in orange. At each tableting time the individual symbols represent the single tablet assays and the line represents the average assay. Red lines represent the level 1 range limits for single tablet assays. The numbers to the right of each plot are the mean assay, the RSD, the minimum and the maximum assays for the 60 tablets overall. 8 Content Uniformity of Direct Compression tablets
9 Figure 2: plots of tablet assays using two mixing schemes and 5 filler-binders Content Uniformity of Direct Compression tablets 9
10 The tabulated data and the plots reveal differences between the two mixing schemes and also between excipients used. When mixing scheme A was employed, only SuperTab 30GR gave acceptable data. For SuperTab 11SD and SuperTab 22AN there were occasional super-potent tablets detected (a total of 3 out of 120 tablets analysed) and it is these tablets that lead to the higher AV results. Two super-potent tablets were detected when SuperTab 21AN was used, and additionally there were slightly high AV results at sampling times when there were no super-potent tablets. Pharmacel 102 shows most clearly how deagglomeration can affect the content uniformity result. When mixing scheme B was employed there were no failures in any of the tablets analysed using any fillerbinder, showing how the sieving step has effectively reduced the agglomerates to a sub-critical level. There is little difference in the data between the different filler-binders. This confirms the importance of the deagglomeration step in direct compression tableting. It is probably no coincidence that the more free flowing excipients (SuperTab 30GR, 11SD and 22AN) give better results than SuperTab 21AN and Pharmacel 102. In the cube mixer used in this study it is likely that the better flowing excipients form a rolling powder bed than can, to some extent, ball mill the paracetamol agglomerates. This probably does not happen when SuperTab 21AN and Pharmacel 102 are used. Note that only the use of the sieving step, or other deagglomeration step, gives assurance that agglomerates have been suitably reduced. Even though use of SuperTab 30GR in mixing scheme A gave acceptable analytical results, it is possible that super-potent tablets were present but not sampled in this trial. Except for occasional super-potent tablets, the overall appearance of the analytical data when a free flowing excipient is used is very similar for both mixing schemes, with an approximate normal distribution of tablets around 100% label strength. This is exemplified in Figure 3 for the SuperTab 22AN tablets. If the single super-potent tablet is excluded, then the RSD given by mixing scheme A is 2.8% compared to 2.5% for mixing scheme B. Thus the small sample size required for pharmacopoeial content uniformity testing may not detect the occasional super-potent tablet in a batch, and lead to false assurance of acceptable content uniformity. Figure 3: Distribution of tablets assays with different mixing schemes 10 Content Uniformity of Direct Compression tablets
11 7 Conclusions Excellent content uniformity of direct compression tablets can be achieved by following 3 guides Ensure that the API has a particle size fine enough to be capable of adequate dispersion. Ensure that the API is adequately dispersed by inclusion of a premix and deagglomeration step in preparation of the compression mix. Use a free flowing excipient to aid agglomerate dispersal, and with surface properties that are favourable for drug adhesion. 8 References Egermann 1982 Definition and conversion of the mean particle diameter referring to mixing homogeneity, H Egermann, Powder Technology. 1982, 31, Rohrs 2005 Particle Size Limits to Meet USP Content Uniformity Criteria for Tablets and Capsules, BR Rohrs, GE Amidon, RH Meury, PJ Secreast, HM King, CJ Skoug, J. Pharm. Sci., 2006, 95, Egermann 1979 : agglomeration during sieving, Sci. Pharm., 1979, 47, (in German) Staniforth 1982 Effect of vibration time, frequency and acceleration on drug content uniformity, JN Staniforth, JE Rees, J. Pharm. Pharmacol., 1982, 34, Staniforth 1986 Order out of chaos, JN Staniforth, J. Pharm. Pharmacol., 1987, 39, Content Uniformity of Direct Compression tablets 11
12 DFE Pharma (#code/month year) 12 Content Uniformity of Direct Compression tablets
Re-compaction properties of lactose and microcrystalline cellulose
Re-compaction properties of lactose and microcrystalline cellulose Individual excipients MCC Starch Lactose Inhalation Superdisintegrants SuperTab 21AN (anhydrous lactose) is the preferred form of lactose
More informationPrimellose is an excellent choice as superdisintegrant in ODT applications
Primellose is an excellent choice as superdisintegrant in ODT applications MCC Starch Lactose Inhalation Superdisintegrants Summary In orally disintegrating tablets, the excipients of choice in direct
More informationInfluence of blender type on the performance of ternary dry powder inhaler formulations
Institute of Pharmacy Kiel University Influence of blender type on the performance of ternary dry powder inhaler formulations Mats Hertel Theoretical background Binary formulation: 1 st blending Ternary
More informationFigure 1: SEM Mannogem EZ (1000x)
Carrier-Mixing of Mannogem EZ with Micronized Low dose Furosemide: Uniformity of dosage unit study Sunil Kumar N *, John K Tillotson, Praveen Saligram, Robert Duffy SPI Pharma Inc. Introduction: To produce
More informationOCE TABLETING DIRECT COMPRESSION CO-PROCESSED LACTOSE. Technical brochure MicroceLac 100
IC OCE TABLETING DIRECT COMPRESSION CO-PROCESSED LACTOSE AC Technical brochure MEGGLE co-processed lactose grades for direct compression: General information Direct compression (DC) tablet manufacture
More informationTechnical brochure StarLac
T R TABLETING AC DIRECT COMPRESSION CO-PROCESSED LACTOSE Technical brochure MEGGLE co-processed lactose grades for direct compression: General information Direct compression (DC) tablet manufacture is
More informationTEPZZ _7584 A_T EP A1 (19) (11) EP A1 (12) EUROPEAN PATENT APPLICATION. (51) Int Cl.: A61K 9/00 ( ) A61K 31/439 (2006.
(19) TEPZZ _784 A_T (11) EP 3 17 842 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: 07.06.17 Bulletin 17/23 (1) Int Cl.: A61K 9/00 (06.01) A61K 31/439 (06.01) (21) Application number: 1197874.9
More informationThe unlocked synergy of DFE Pharma MCC
The unlocked synergy of DFE Pharma MCC We are DFE Pharma We are the global leader in excipient solutions. We develop, produce and market excipients for oral solid dose and dry powder inhalation formulations.
More informationSTARCH Application Data
STARCH 1500 Application Data Partially Pregelatinized Maize Starch Starch 1500, Partially Pregelatinized Maize Starch, Used as a Binder Disintegrant in High Shear Wet Granulation Comparison to Povidone
More informationYOUR ORAL SOLID DOSE. In pursuit of excipient excellence
YOUR ORAL SOLID DOSE DFE Pharma globally supplies a unique, broad portfolio of key excipients including lactose, MCC, superdisintegrants and starches. Innovative products such as SuperTab 24AN and SuperTab
More informationLubriTose Mannitol Michael Crowley, Director of R&D, Excipients
LubriTose Mannitol Michael Crowley, Director of R&D, Excipients Introduction Michael Crowley Director of R&D Excipients 158 St. Highway 320 Norwich, NY 13815 PH 315-802-5970 Michael.Crowley@Kerry.com 2
More informationAssessment of Low Dose Content Uniformity of Indomethacin in Excipient Blends Using FT-Raman Mapping Spectroscopy
Starch 1500 Application Data Partially Pregelatinized Maize Starch Assessment of Low Dose Content Uniformity of Indomethacin in Excipient Blends Using FT-Raman Mapping Spectroscopy OBJECTIVE To characterize
More informationSTUDY OF THE DETERIORATION OF ASPIRIN IN THE PRESENCE OF VARIOUS EXCIPIENTS
STUDY OF THE DETERIORATION OF ASPIRIN IN THE PRESENCE OF VARIOUS EXCIPIENTS D.L.D.A.N DAHANAYAKA, A. MUNISINGHE, D.T.U. ABEYTUNGA DEPARTMENT OF CHEMISTRY, UNIVERSITY OF COLOMBO Abstract Aspirin is a non
More informationFLORITER. New Technology for Innovative Formulation Design.
FLORITER New Technology for Innovative Formulation Design www.tomitaph.co.jp FLORITE Dramatically Change Your Formulation FLORITE is synthetic Calcium Silicate with exceptional liquid absorbency and excellent
More informationAvailable online Research Article
Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 26, 8(2):7-7 Research Article ISSN : 975-7384 CODEN(USA) : JCPRC5 Optimization of directly compressible mixtures of microcrystalline
More informationEverything for Inhalation
Everything for Inhalation Everything for Inhalation Inhalation drug product development at Hovione has a strong focus on formulation for Dry Powder Inhalers (DPI), particularly for capsule-based and reservoir-based
More informationTechnical brochure CombiLac
OM I AC TABLETING DIRECT COMPRESSION CO-PROCESSED LACTOSE Technical brochure MEGGLE co-processed lactose grades for direct compression: General information Direct compression (DC) tablet manufacture is
More informationThe influence of lactose particle size on dry powder inhalation performance
The influence of lactose particle size on dry powder inhalation performance MCC Starch Lactose Inhalation Superdisintegrants 1 Introduction In most dry powder inhalation (DPI) formulations carriers are
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 informationSCIENTIFIC DISCUSSION
SCIENTIFIC DISCUSSION Name of the Finished Pharmaceutical Product: Manufacturer of Prequalified Product: Active Pharmaceutical Ingredients (APIs): Pharmaco-therapeutic group (ATC Code): Therapeutic indication:
More informationEffect of Compaction Forces on Powder Bed Permeability of Magnesium Silicate "Common Excipient Mixture"
Effect of Compaction Forces on Powder Bed Permeability of Magnesium Silicate "Common Excipient Mixture" SAMEER AL-ASHEH a, FAWZI BANAT a, ALA A SALEM a, IAD RASHID b, ADNAN BADWAN b a Department of Chemical
More informationFORMULATION AND DEVELOPMENT OF ER METOPROLAOL SUCCINATE TABLETS
International Journal of PharmTech Research CODEN( USA): IJPRIF ISSN : 0974-4304 Vol.1, No.3, pp 634-638, July-Sept 2009 FORMULATION AND DEVELOPMENT OF ER METOPROLAOL SUCCINATE TABLETS K. Reeta Vijaya
More informationVolume: 2: Issue-3: July-Sept ISSN FORMULATION AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF NICORANDIL
Volume: 2: Issue-3: July-Sept -2011 ISSN 0976-4550 FORMULATION AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF NICORANDIL Ajaykumar Patil*, Ashish Pohane, Ramya Darbar, Sharanya Koutika, Alekhya
More informationSCIENTIFIC DISCUSSION. Efavirenz
SCIENTIFIC DISCUSSION Name of the Finished Pharmaceutical Product: Manufacturer of Prequalified Product: Active Pharmaceutical Ingredient (API): Pharmaco-therapeutic group (ATC Code): Therapeutic indication:
More informationFormulation and evaluation of oro-dispersible tablets of lafutidine
Available online at www.scholarsresearchlibrary.com Scholars Research Library Der Pharmacia Lettre, 2015, 7 (5):226-235 (http://scholarsresearchlibrary.com/archive.html) ISSN 0975-5071 USA CODEN: DPLEB4
More informationPharma & Food Solutions. POLYOX TM Water Soluble Resins Combining Flexibility with Consistency
Pharma & Food Solutions POLYOX TM Water Soluble Resins Combining Flexibility with Consistency POLYOX 9-13 POLYOX 9-13 POLYOX * are nonionic poly (ethylene oxide) polymers that meet all the specifications
More informationLactose Free, Direct Compression Formulation Used to Produce Loratadine (10 mg) Tablets
Technical Data Direct Compression Loratadine Formulation Lactose Free, Direct Compression Formulation Used to Produce Loratadine (10 mg) Tablets INTRODUCTION Loratadine is a popular over-the-counter, nonsedating
More informationTechnical brochure InhaLac
N A DRY POWDER INHALATION SIEVED/MILLED/MICRONIZED LACTOSE AC Technical brochure MEGGLE s, milled and alpha-lactose monyhydrate for dry powder : General information The delivery of active pharmaceutical
More informationReceived: ; Revised; Accepted: PROCESS VALIDATION OF FORMOTEROL FUMARATE AND BUDESONIDE DRY POWDER INHALATION
International Journal of Institutional Pharmacy and Life Sciences 2(5): September-October 2012 INTERNATIONAL JOURNAL OF INSTITUTIONAL PHARMACY AND LIFE SCIENCES Pharmaceutical Sciences Original Article!!!
More informationGranulation Aggregation
Granulation Aggregation Wet granulation Solvent granulation (crust granules) Binder granulation (sticked granules) Granulation liquid Water Water + alcohol mixture Macromolecular colloidal solution i.e.:
More informationThe binding performance of DFE Pharma Starch
The binding performance of DFE Pharma Starch MCC Starch Lactose Inhalation Superdisintegrants We are DFE Pharma We are the global leader in excipient solutions. We develop, produce and market excipients
More informationDESIGN AND EVALUATION OF CONTROLLED RELEASE MATRIX TABLETS OF FLURBIPROFEN
Int. J. Chem. Sci.: 10(4), 2012, 2199-2208 ISSN 0972-768X www.sadgurupublications.com DESIGN AND EVALUATION OF CONTROLLED RELEASE MATRIX TABLETS OF FLURBIPROFEN K. V. R. N. S. RAMESH *, B. HEMA KIRNAMAYI
More informationNarrowing the gap between clinical capsule formulations and commercial film-coated tablets
Narrowing the gap between clinical capsule formulations and commercial film-coated tablets Based on formulation simplicity and blinding capability, hard gelatin capsules are preferrable compared with other
More information(51) Int Cl.: A61K 9/20 ( ) A61K 31/41 ( )
(19) TEPZZ 94677_A_T (11) (12) EUROPEAN PATENT APPLICATION (43) Date of publication: 2.11.1 Bulletin 1/48 (1) Int Cl.: A61K 9/ (06.01) A61K 31/41 (06.01) (21) Application number: 116790.3 (22) Date of
More informationThe Relevance of USP Methodology in the Development of a Verapamil Hydrochloride (240 mg) Extended Release Formulation
METHOCEL Premium Cellulose Ethers Application Data The Relevance of USP Methodology in the Development of a Verapamil Hydrochloride (240 mg) Extended Release Formulation INTRODUCTION Hydrophilic matrices
More informationDEVELOPMENT AND EVALUATION OF A DIRECTLY COMPRESSIBLE CO PROCESSED MULTIFUNCTION SUSTAINED RELEASE AGENT FOR TABLETS
International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 975-1491 Vol 2, Suppl 4, 1 Research Article DEVELOPMENT AND EVALUATION OF A DIRECTLY COMPRESSIBLE CO PROCESSED MULTIFUNCTION SUSTAINED
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 informationIngredients adapted to a fit for use model. APIs allowed the fit for use strategy to work. There has been a shift to designed for purpose
1 Pharmaceutical industry borrowed ingredients from other industries Food Cosmetic Industrial Ingredients adapted to a fit for use model. APIs allowed the fit for use strategy to work that has all changed
More informationInt. Res J Pharm. App Sci., 2014; 4(1):47-51 ISSN:
International Research Journal of Pharmaceutical and Applied Sciences (IRJPAS) Available online at www.irjpas.com Int. Res J Pharm. App Sci., 2014; 4(1):47-51 Research Article FORMULATION AND EVALUATION
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 informationREVISION OF MONOGRAPH ON TABLETS. Tablets
March 2011 REVISION OF MONOGRAPH ON TABLETS Final text for addition to The International Pharmacopoeia This monograph was adopted by the Forty-fourth WHO Expert Committee on Specifications for Pharmaceutical
More informationTECHNICAL INFORMATION RxCIPIENTS FM A versatile excipient for orally disintegrating tablet (ODT) formulations
TECHNICAL INFORMATION 1426 RxCIPIENTS FM 1 A versatile excipient for orally disintegrating tablet (ODT) formulations Table of contents 1 Introduction 3 2 Mode of action and advantages of RxCIPIENTS FM
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 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 informationExcipient Functionality & Pharmacopoeia IPEC Europe Excipients Forum Nice, 5 February 2015
Excipient Functionality & Pharmacopoeia IPEC Europe Excipients Forum Nice, 5 February 2015 Dr. Susanne Keitel Director EDQM, Council of Europe Outline 1. The European Pharmacopoeia 2. The importance of
More informationINTEGRATED DESIGN SPACE TO DEVELOP BETTER DPI FORMULATIONS
INTEGRATED DESIGN SPACE TO DEVELOP BETTER DPI FORMULATIONS Here, Filipa Maia, PhD, and Maria Palha, MSc, both Scientists at Hovione, report a study whose objective was to establish relationships between
More informationJ.Ayyappan et al, /J. Pharm. Sci. & Res. Vol.2 (7), 2010,
Development and Evaluation of a Directly Compressible Co-processed Multifunction Sustained Release Agent for Gliclazide Sustained Release Tablets J. Ayyappan* 1, P.Umapathi 1, Darlin Quine 2 1 Department
More informationFormulation and evaluation of sublingual tablets of lisinopril
Journal of GROVER Scientific & Industrial AGARWAL: Research FORMULATION AND EVALUATION OF SUBLINGUAL TABLETS OF LISINOPRIL Vol. 71, June 2012, pp. 413-417 413 Formulation and evaluation of sublingual tablets
More information(12) Patent Application Publication (10) Pub. No.: US 2003/ A1
US 2003.01.18647A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0118647 A1 Seth (43) Pub. Date: (54) EXTENDED RELEASE TABLET OF Publication Classification METFORMIN (51)
More informationINTERNATIONAL RESEARCH JOURNAL OF PHARMACY ISSN Research Article
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY www.irjponline.com ISSN 2230 8407 Research Article FORMULATION AND EVALUATION OF PRAVASTATIN SODIUM IMMEDIATE RELEASE TABLETS Devanand Pinate 1 *, Ravikumar 1,
More informationJournal of Chemical and Pharmaceutical Research
Available on line www.jocpr.com Journal of Chemical and Pharmaceutical Research J. Chem. Pharm. Res., 2010, 2(5):534-540 ISSN No: 0975-7384 CODEN(USA): JCPRC5 Formulation and evaluation of Valsartan film
More informationDistribution of low dose drugs in granules: Influence of method of incorporation
Available online at www.scholarsresearchlibrary.com Scholars Research Library Archives of Applied Science Research, 2011, 3 (3):241-245 (http://scholarsresearchlibrary.com/archive.html) ISSN 0975-508X
More informationWettable Magnesium Stearate. What Are Customers Looking for in Selecting Pharmaceutical Lubricants?
Wettable Magnesium Stearate Presented By: Richard Pudlo P.E. Principal Chemical Engineer April 29 th, 2015 What Are Customers Looking for in Selecting Pharmaceutical Lubricants? Meet USP/.NF monograph
More informationSTARCH Proven and Trusted Excipient for Performance and Versatility EXCIPIENTS. Effective and economical disintegrant
EXCIPIENTS STARCH 1500 Proven and Trusted Excipient for Performance and Versatility Effective and economical disintegrant Excellent stability for moisture sensitive drugs Manufactured exclusively for the
More informationDirect Compression Formulation Using Starch 1500 with Ranitidine HCl (150 mg) Tablets, Film Coated with Opadry II (85F Series)
Technical Data Direct Compression Ranitidine Formulation Direct Compression Formulation Using Starch 15 with Ranitidine HCl (15 mg) Tablets, Film Coated with Opadry II (5F Series) INTRODUCTION Ranitidine
More informationShort Communication. Formulation of Furosemide Dispersible Tablets for Use in Paediatrics V. V. ABWOVA, P. N. MBEO, L. J. TIROP AND K. A. M.
61 East and Central African Journal of Pharmaceutical Sciences Vol. 18 (2015) 61-66 Short Communication Formulation of Furosemide Dispersible Tablets for Use in Paediatrics V. V. ABWOVA, P. N. MBEO, L.
More informationAvailable online through
Research Article Available online through www.ijrap.net DESIGN AND EVALUATION OF LOW COST DIRECTLY COMPRESSIBLE EXCIPIENTS Swamy P. V. *, Patil A. N., Shirsand S. B., Amitkumar T., Laeeq Farhana H.K.E
More informationInt. Res J Pharm. App Sci., 2013; 3(6):42-46 ISSN:
International Research Journal of Pharmaceutical and Applied Sciences (IRJPAS) Available online at www.irjpas.com Int. Res J Pharm. App Sci., 2013; 3(6):42-46 Research Article ENHANCEMENT OF SOLUBILITY
More informationPreformulation Study. CHAPTER 3 Preformulation Study. 3.0 Introduction
CHAPTER 3 3.0 Introduction As per Sir Arthur Conan Doyle, It is a capital mistake to theorize before one has data. Preformulation work is the foundation for development of any robust formulations (G. Banker
More informationFormulation and Evaluation
Chapter-5 Formulation and Evaluation 5.1 OBJECTIVE After successful taste masking and solubility enhancement of drugs in preliminary studies, by using Mannitol Solid Dispersion, next step includes the
More informationThe Particle Design of Cellulose and the Other Excipients for a Directly Compressible Filler-Binder
The Particle Design of Cellulose and the Other Excipients for a Directly Compressible Filler-Binder Hiroto Miyamoto KNOWKATSU 1 Abstract Cellulose and saccharide are commonly used filler-binder. This summary
More informationSUSTAINED RELEASE TABLETS USING A PVA DC FORMULATION RESISTANT TO ALCOHOL INDUCED DOSE DUMPING
SUSTAINED RELEASE TABLETS USING A PVA DC FORMULATION RESISTANT TO ALCOHOL INDUCED DOSE DUMPING Dr. Dieter Lubda MilliporeSigma is a business of Merck KGaA, Darmstadt, Germany Agenda: Sustained release
More informationDirect Compression. With the right ingredients it s a simple, cost-effective manufacturing process
Direct With the right ingredients it s a simple, cost-effective manufacturing process TM Trademark of The Dow Chemical Company ( Dow ) or an affiliated company of Dow Speed and savings sounds good to us
More informationINTERNATIONAL RESEARCH JOURNAL OF PHARMACY ISSN Research Article
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY www.irjponline.com ISSN 2230 8407 Research Article FORMULATION AND EVALUATION OF IMMEDIATE RELEASE VENLAFAXINE HCL TABLETS: COMPARATIVE STUDY OF SUPER DISINTEGRANT
More informationPacking and cohesive properties of some locally extracted starches
Research Article Itiola and Odeku Tropical Journal of Pharmaceutical Research, June 2005; 4 (1): 363-368 Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria. All rights
More informationMathivanan. N et al, JGTPS, 2015, Vol. 6(2):
ISSN: 2230-7346 Mathivanan N et al. / JGTPS / 6(2)-(2015) 2611 2620 (Research Article) Journal of Global Trends in Pharmaceutical Sciences Journal home page: www.jgtps.com EFFECT OF MICROCRYSTALLINE CELLULOSE
More informationFormulation and In-vitro Evaluation of Chewable Tablets of Montelukast Sodium
Available online on www.ijddt.com International Journal of Drug Delivery Technology 214; (3); 98-13 Research Article ISSN: 97 441 Formulation and In-vitro Evaluation of Chewable Tablets of Montelukast
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 informationInternational Journal of Research in Pharmaceutical and Nano Sciences Journal homepage:
Review Article CODEN: IJRPJK ISSN: 2319 9563 International Journal of Research in Pharmaceutical and Nano Sciences Journal homepage: www.ijrpns.com ADVANCED GRANULATION TECHNIQUES FOR PHARMACEUTICAL FORMULATIONS
More informationFABRICATION AND EVALUATION OF GLIMEPIRIDE CORDIA DICHOTOMA G.FORST FRUIT MUCILAGE SUSTAINED RELEASE MATRIX TABLETS
Int. J. Chem. Sci.: 7(4), 2009, 2555-2560 FABRICATION AND EVALUATION OF GLIMEPIRIDE CORDIA DICHOTOMA G.FORST FRUIT MUCILAGE SUSTAINED RELEASE MATRIX TABLETS HINDUSTAN ABDUL AHAD *, B. PRADEEP KUMAR, C.
More informationDEVELOPMENT OF NON SODIUM EFFERVESCENT TABLET OF PARACETAMOL USING ARGININE CARBONATE
IJPSR (2013), Vol. 4, Issue 5 (Research Article) Received on 17 July, 2012; received in revised form, 23 February, 2013; accepted, 14 April, 2013 DEVELOPMENT OF NON SODIUM EFFERVESCENT TABLET OF PARACETAMOL
More informationContinuous Granulation Using a Twin-Screw Extruder. Lin Zhu, Ph.D. Manufacture Science and Technology AbbVie June, 2016
Continuous Granulation Using a Twin-Screw Extruder Lin Zhu, Ph.D. Manufacture Science and Technology AbbVie June, 2016 What is a twin screw extruder and how to use it for continuous granulation? Dry feed:
More informationFORMULATION AND EVALUATION OF VALSARTAN TABLETS EMPLOYING CYCLODEXTRIN-POLOXAMER 407-PVP K30 INCLUSION COMPLEXES
Int. J. Chem. Sci.: 10(1), 2012, 297-305 ISSN 0972-768X www.sadgurupublications.com FORMULATION AND EVALUATION OF VALSARTAN TABLETS EMPLOYING CYCLODEXTRIN-POLOXAMER 407-PVP K30 INCLUSION COMPLEXES K. P.
More informationIJRPC 2012, 2(3) Chowdary 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 PREPARATION, CHARACTERIZATION AND EVALUATION OF PGS - PVP CO-PROCESSED EXCIPIENT AS DIRECTLY
More informationFormulation And Evaluation Of Flurbiprofen Matrix Tablets For Colon Targeting
Formulation And Evaluation Of Flurbiprofen Matrix Tablets For Colon Targeting Biresh Kumar Sarkar* 1, Devananda Jain 1, Mamta Parwal 2 1. Bhagwant University, Dept.of Pharmaceutical Tech and Sciences,
More informationCOMPARATIVE EFFECT OF DIFFERENT HIGH FUNCTIONALITY EXCIPIENTS ON VARIOUS CHARACTERISTICS OF VARDENAFIL HCL TABLETS (BCS II DRUG)
IJPSR (2014), Vol. 5, Issue 12 (Research Article) Received on 27 April, 2014; received in revised form, 28 July, 2014; accepted, 08 August, 2014; published 01 December, 2014 COMPARATIVE EFFECT OF DIFFERENT
More informationDrug Development by Government Pharmaceutical Organization. Dr. Rachaneekorn Jevprasesphant The Government Pharmaceutical Organization (GPO) Thailand
Drug Development by Government Pharmaceutical Organization Dr. Rachaneekorn Jevprasesphant The Government Pharmaceutical Organization (GPO) Thailand 20August 2012 GPO s Profile GPO was established in 1966.
More informationEP A1 (19) (11) EP A1 (12) EUROPEAN PATENT APPLICATION. (43) Date of publication: Bulletin 2009/42
(19) (12) EUROPEAN PATENT APPLICATION (11) EP 2 8 36 A1 (43) Date of publication: 14..09 Bulletin 09/42 (21) Application number: 084239.1 (1) Int Cl.: A61K 9/16 (06.01) A61K 9/ (06.01) A61K 31/4178 (06.01)
More informationAdopting Technologies to Enhance Quality in Manufacturing
Adopting Technologies to Enhance Quality in Manufacturing Sandip B. Tiwari, Ph.D. March 18, 2012 Current Status of Quality in Pharma Manufacturing Pharmaceutical manufacturing techniques lag behind those
More informationFormulation and evaluation of immediate release salbutamol sulphate
5 Formulation, optimization and evaluation of immediate release layer of salbutamol sulphate Salbutamol is moderately selective beta (2)-receptor agonist similar in structure to terbutaline and widely
More informationApplication of Starches, Modified Starches and Starch Derivatives in Pharmaceutical Products
57. Starch Convention, Detmold, April 26-28, 2006 K.-J. Steffens Application of Starches, Modified Starches and Starch Derivatives in Pharmaceutical Products Starches, Pharmaceutical Applications _ Starches
More informationFormulation Development and Evaluation of Antidiabetic Polyherbal Tablet
Research Article Formulation Development and Evaluation of Antidiabetic Polyherbal Tablet Komal Patel 1*, Lal Hingorani 2, Vinit Jain 3 1 School of Pharmacy, RK University, Rajkot and Parul Institute of
More informationSCIENTIFIC DISCUSSION
This part reflects the scientific knowledge and the information about this product available at the time of prequalification. Thereafter, updates may have become necessary which are included in parts 1
More informationFORMULATION AND EVALUATION OF PIROXICAM AND CELECOXIB TABLETS EMPLOYING PROSOLVE BY DIRECT COMPRESSION METHOD
Int. J. Chem. Sci.: 6(3), 2008, 1270-1275 FORMULATION AND EVALUATION OF PIROXICAM AND CELECOXIB TABLETS EMPLOYING PROSOLVE BY DIRECT COMPRESSION METHOD K. P. R. CHOWDARY, P. TRIPURA SUNDARI and K. SURYA
More informationINTERNATIONAL RESEARCH JOURNAL OF PHARMACY ISSN Research Article
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY www.irjponline.com ISSN 2230 8407 Research Article FORMULATION AND EVALUATION OF LOSARTAN POTASSIUM AND HYDROCHLORTHIAZIDE CONVENTIONAL RELEASE TABLETS Devareddy
More informationThe Effect of Film Coating and Storage Conditions on the Performance of Metformin HCl 500 mg Extended Release Hypromellose Matrices
METHOCEL Application Data Premium Cellulose Ethers The Effect of Film Coating and Storage Conditions on the Performance of Metformin HCl 500 mg Extended Release Hypromellose Matrices ABSTRACT SUMMARY This
More informationAvailable online Research Article
Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2014, 6(12):213-221 Research Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 Formulation development and evaluation of metoprolol
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 informationINTERNATIONAL RESEARCH JOURNAL OF PHARMACY
INTERNATIONAL RESEARCH JOURNAL OF PHARMACY www.irjponline.com ISSN 2230 8407 Research Article FORMULATION DEVELOPMENT AND EVALUATION OF IMMEDIATE RELEASE BILAYER TABLETS OF TELMISERTAN AND HYDROCHLOROTHIAZIDE
More informationFormulation Development and Evaluation of Cholecalciferol (Vitamin D3) Granules and Tablets
Journal of Chronotherapy and Drug Delivery ORIGINAL RESEARCH PAPER Formulation Development and Evaluation of Cholecalciferol (Vitamin D3) Granules and Tablets Manohar Urankar*, Naveen Reddy, Vijay Ranka
More informationSCIENTIFIC DISCUSSION. Antimycobacterial (J04AC01).
SCIENTIFIC DISCUSSION Name of the Finished Pharmaceutical Product: Manufacturer of Prequalified Product: Active Pharmaceutical Ingredients (APIs): International Nonproprietary Name: Pharmaco-therapeutic
More informationIntroduction. Nwoko Valentine E
Research Article Introduction Journal of Pharmaceutics & Drug Development Volume Issue 4 ISSN: 348-978 Open Access Croscarmellose Sodium Efficiency in the Development of a Generic Capsule Formulation of
More informationAvailable online through ISSN
Research Article Available online through www.ijrap.net ISSN 2229-3566 FORMULATION AND EVALUATION OF ORO DISPERSIBLE TABLETS OF METOPROLOL TARTRATE BY DIRECT COMPRESSION USING SUPER DISINTEGRANTS A. Senthil*
More informationSivakasi , Tamil Nadu, India. ABSTRACT KEYWORDS:
276 P a g e International Standard Serial Number (ISSN): 2319-8141 International Journal of Universal Pharmacy and Bio Sciences 4(1): January-February 2015 INTERNATIONAL JOURNAL OF UNIVERSAL PHARMACY AND
More informationFormulation and Evaluation of Rosuvastatin Immediate Release Tablets 10 Mg
IOSR Journal of Pharmacy and Biological Sciences (IOSR-JPBS) e-issn:2278-3008, p-issn:2319-7676. Volume 11, Issue 5 Ver. III (Sep. - Oct.2016), PP 01-05 www.iosrjournals.org Formulation and Evaluation
More informationDesigned and manufactured specifically for pharmaceutical capsule filling
EXCIPIENTS Designed and manufactured specifically for pharmaceutical capsule filling Simple formulation Superior flow and weight uniformity Clean and efficient processing This document is valid at the
More informationCompression and Mechanical Properties of Tablet Formulations
Compression and Mechanical Properties of Tablet Formulations Containing Corn, Sweet, and Starches as Binders O.A. Odeku*, O.O. Awe, B. Popoola, M.A. Odeniyi, and O.A. Itiola The authors study the effects
More informationQ&A for submission of applications for prequalification of Zinc Sulfate tablets and Zinc Sulfate oral liquid (solution)
Q&A for submission of applications for prequalification of Zinc Sulfate tablets and Zinc Sulfate oral liquid (solution) This document should not be treated as a comprehensive guideline; it serves as a
More informationVolume: I: Issue-2: Aug-Oct ISSN NOVEL APPROACH IN FORMULATION AND EVALUATION OF MOUTH DISSOLVING TABLETS OF ONDANSETRON HYDROCHLORIDE
Volume: I: Issue-2: Aug-Oct -2010 ISSN 0976-4550 NOVEL APPROACH IN FORMULATION AND EVALUATION OF MOUTH DISSOLVING TABLETS OF ONDANSETRON HYDROCHLORIDE * Hindustan Abdul Ahad, Anuradha CM, Chitta Suresh
More information