FORMULATION DEVELOPMENT AND EVALUATION OF FINGOLIMOD CAPSULES BY ORAL DRUG DELIVERY

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1 WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES Venkatesh et al. SJIF Impact Factor Volume 5, Issue 9, Research Article ISSN FORMULATION DEVELOPMENT AND EVALUATION OF FINGOLIMOD CAPSULES BY ORAL DRUG DELIVERY G. Venkatesh *, S. Poonguzhali and Manohar Babus Department of Pharmaceutics, SIMS College of Pharmacy, SIMS Group of Institutions, Mangaldas Nagar, Guntur, , Andhra Pradesh, India. Article Received on 18 July 2016, Revised on 07 August 2016, Accepted on 27 August 2016 DOI: /wjpps *Corresponding Author G. Venkatesh Department of Pharmaceutics, SIMS College of Pharmacy, SIMS Group of Institutions, Mangaldas Nagar, Guntur, , Andhra Pradesh, India. ABSTRACT The study was undertaken with an aim to develop an optimized formulation of Fingolimod capsules by oral drug delivery. The active pharmaceutical ingredient, Fingolimod was selected and formulated as capsule contained 0.50 mg of Fingolimod Comparable to the innovators product. Capsules were prepared by using wet granulation technique. Finished products were evaluated for disintegration time, assay, and In-vitro release studies. The developed trials were tested for In-vitro dissolution profile and compared with the reference product. The In-vitro dissolution profile of formula7 was similar to that of reference product. The optimized batch capsules were packed in HDPE containers and performed stability studies at 40 C/75%RH and 25 C / 60% RH. All the results were found to be satisfactory. Hence the designed and developed formula of Fingolimod was stable. The objective of the present project was successfully achieved by developing the product, giving the same release profile to that of innovators product. KEYWORDS: Fingolimod capsules, Reference product, Dissolution profile, stability studies. 1. INTRODUCTION The goal of any drug delivery system is to provide a therapeutic amount of drug in the proper site in the body to achieve promptly and then to maintain the desired drug concentration. That is, the drug delivery system should deliver drug at a rate dedicated by the needs of the body over a specified period of treatment. [1] Vol 5, Issue 9,

2 1.1 Oral drug delivery Oral dosage forms such as capsules are considered the most Patient acceptable dosage forms available today. Not only do they offer convenience and ease of handling, but also they are extremely stable (chemical and physical), have a high throughput and are relatively inexpensive to produce. Orally administered dosage forms are an intricate blend of pharmaceutical excipients and active pharmaceutical ingredients (APIs) that must be adequately mixed and/or granulated to ensure the manufacture of acceptable pharmaceutical products.pharmaceutical granulation is often necessary to overcome the significant compression difficulties and erratic flow properties of many APIs; characteristics that often limit the successful production of acceptable dosage forms. Although pharmaceutical granulation is often necessary, it is a batch process that provides a bottleneck for the implementation of continuous manufacturing for orally administered solid dosage forms. [2] Oral route of drug administration have wide acceptance up to 50-60% of total dosage forms. Solid dosage forms are popular because of ease of administration, accurate dosage, self medication, pain avoidance and most importantly patient compliance. The most popular solid dosage forms are tablets and capsules [3] 1.2 CAPSULES [4] Fig: 1.Capsules Capsules are gelatin shells filled with the ingredients that make up an individual dose. Dry powders, semi-solids, and liquids that do not dissolve gelatin may be encapsulated. Capsules account for about 20% of all prescriptions dispensed. Contents of Capsules [5-8] Gelatin It is the major component of the capsule. There are two main types of gelatin: Type A: produced by acid hydrolysis of animal skins. Type B: produced by basic hydrolysis of bovine bones. Vol 5, Issue 9,

3 Gelatin possesses five basic properties: 1. Non-toxic, 2. Soluble in biological fluids at body temperature, 3. It is a good film-forming material, 4. Solutions of high concentration, 40% w/v, are mobile at 50 C, 5.A solution in water changes from a sol to a gel at temperatures only a few degrees above ambient (Others require volatile solvents or large quantities of heat) [9-10] Colorants: There are two types [10-12] I. water soluble dyes e.g. erythrosine II. pigments e.g. iron oxides, titanium dioxide (make the capsule opaque to provide protection against light) Preservatives 2. DRUG PROFILE Fig No: 2 Structure of Fingolimod Systematic (IUPAC) name: 2-amino-2-[2-(4-octylphenyl) ethyl]propane-1,3-diol Formula: C 19 H 33 NO 2 Molecular mass: g/mol Table No: 1. Pharmacokinetics of Drug Vol 5, Issue 9,

4 3. MATERIALS AND METHODS Table no: 2 List of materials used for Formulation of Fingolimod Hcl capsules. Table no: 3 List Of Equipments/Instruments Used In Formulation process Vol 5, Issue 9,

5 4. RESULTS AND DISCUSSIONS Table no: 4 Formulation Design of Fingolimod: Fig no. 3 FTIR spectrum of fingolimod Fig no.4 FT IR spectrum of fingolimod with Microcrystalline Cellulose ((MCCC)) Vol 5, Issue 9,

6 Fig no.5 FT IR Spectrum of fingolimod with magnesium stearate Fig no.6 FT IR spectrum of fingolimod with mannitol Fig no.7 FT IR spectrum of F7 Formulation Vol 5, Issue 9,

7 Table No: 5 Result of Drug Excipients Compatibility Studies Table: 6 Micromeritic properties of fingolimod capsules Vol 5, Issue 9,

8 Table: 7 Evaluation parameters of fingolimod capsules Table No: 8 Dissolution prof ile of Fingolimod capsules (F1) Fig No: 8 Dissolution profile of Fingolimod capsules (F1) Vol 5, Issue 9,

9 Table No: 9 Dissolution profile of Fingolimod capsules (F2) Fig No: 9 Dissolution profile of Fingolimod capsules (F2) Table No: 10 Dissolution profile of Fingolimod capsules(f3) Vol 5, Issue 9,

10 Fig No: 10 Dissolution profile of Fingolimod capsules (F3) Table No: 11 Dissolution profile of Fingolimod capsules(f4) Fig No: 11 Dissolution profile of Fingolimod capsules (F4) Vol 5, Issue 9,

11 Table No: 12 Dissolution profile of Fingolimod capsules(f5) Fig No: 12 Dissolution profile of Fingolimod capsules (F5) Table No: 13 Dissolution profile of Fingolimod capsules(f6) Vol 5, Issue 9,

16 Fig No: 19 Dissolution profile of Fingolimod capsules (F12) Table No: 20 Comparative drug release profile of F7 with Innovators product Fig No: 20 Comparative drug release profile of F7 with Innovator Vol 5, Issue 9,

17 Table no: 21 kinetic studies of Fingolimod capsules Fig No: 21 Graph for the formulation F7-Zero Order Kinetics Fig No: 22 Graph for the formulation F7-First Order Kinetics Vol 5, Issue 9,

18 Fig No: 23 Graph for the formulation F7-Higuchi model Fig No: 24 Graph for the formulation F7- Korse Meyer Peppas model Table no: 22 Physical evaluation for stability studies of optimized formulations (F7) at 400C / 75% RH for 1, 2 and 3months Vol 5, Issue 9,

19 Table no: 23 Cumulative release of stability studies of optimized formulation (F7) at 40 0 C /75% RH for 1, 2 and 3months Fig No: 25 Dissolution profiles for 1, 2 and 3months stability samples at 40 O C / 75% RH Table no: 24 Physical evaluation for stability studies of optimized formulation (F7) at 25 0 C/ 60% RH for three month Fig No: 26 Dissolution profiles for 3 months stability samples at 250C / 60% RH Vol 5, Issue 9,

20 Table No: 25 Percentage Cumulative release of stability studies of optimized formulation (F7) at 25 0 C / 60% RH for three month 5. SUMMARY AND CONCLUSION The study was undertaken with an aim to develop an optimized formulation of Fingolimod capsules by oral drug delivery. The active pharmaceutical ingredient, Fingolimod was selected and formulated as capsule contained 0.50mg of Fingolimod Comparable to the innovators product. In the present work, preformulation studies were conducted to know the drug excipients compatibilities. Based on the results, suitable excipients were selected for formulation development. Capsules were prepared by using wet granulation technique. During development of formula, various in process tests such as bulk density, tapped density, Haussner s ratio, compressibility index were evaluated and then weight variation, disintegration time were evaluated for granules. Finished products were evaluated for disintegration time, assay, and In-vitro release studies. The developed trials were tested for In-vitro dissolution profile and compared with the reference products of Gilenya. The In-vitro dissolution profile of formula7 was similar to that of reference product.the optimized batch capsules were packed in HDPE containers and performed stability studies at 40 C/75%RH and 25 C / 60% RH. Stability samples were evaluated initially and after one, two and three months. The results were compared with the pre determined specifications. All the results were found to be satisfactory. Hence the designed and developed formula of Fingolimod was stable. The objective of the present project was successfully achieved by developing the product, giving the same release profile to that of innovators product. 6. BIBLIOGRAPHY 1. Advances in solid dosage form manufacturing technology. Gavin P Andrews Phil. Trans. R. Soc. A 2007; 365: doi: /rsta Aulton M.E, Pharmaceutics: The science of dosage form design, 2nd ed. Churchill Livingstone, London: (2002); P , Brahmankar, D M., Jaiswal, S B., Biopharmaceutics and Pharmacokinetics a treatise. 2003; Reprint of 1st Edition. Published by Jain, M K., Vallabh Prakashan. Delhi P. Vol 5, Issue 9,

21 4. The pharmaceutics and compounding laboratory sequence at the unc ,p Text book of capsules,p World Health Organization document QAS/09.339/final march 2011 revision of monograph capsules,p Colifornia veterinary supply,supplying quality veterinary products since1981, 8. Lachman L. and Lieberman H.A., Pharmaceutical Dosage Forms, In; Tablets, Vol. 2, Marcel Dekker, Inc., New York. 9. Indian Pharmacopoeia, (1996), Controller of publications, Delhi, India, Vol-II, A-146-A Evaluationofcommercialcapsules,uqci.edu.sa/files2/tiny_mce/plugins/filemanager/../capsul es.pdf. 11. Dissolution [ online] Available from single piece and double piece. 13. Brahmaiah Bonthagarala, Sreekanth Nama, Sudarshan Donthiboina, Formulation and Evaluation of Sustained Release Matrix Tablets of Ozacarbazepine by Using Various Polymers, Singapore Journal of Pharmaceutical Research, e-issn No , Print ISSN NO , 2014; 1(1): Brahmaiah.B, Prasanna Kumar Desu, Sreekanth Nama, S.Satish Babu, Formulation and evaluation of extended release mucoadhesive microspheres of simvastatin, International Journal of Pharmaceutical and biomedical Research, ISSN No , March 2013; 4(1): Vol 5, Issue 9,