Sains Malaysiana 39(5)(2010): 737–745

Sifat Fizikal dan Kajian In Vitro Tablet Matriks Pelepasan Tertahan Ketoprofen

(Physical Properties and In Vitro Studies of Sustained-Release  Ketoprofen Matrix Tablets)

Ibrahim Ijang

Bahagian Teknologi Perubatan, Agensi Nuklear Malaysia, Bangi

43000 Kajang, Selangor D.E., Malaysia

Mohd Cairul Iqbal Mohd Amin*, Bukhori Abu Bakar

Fakulti Farmasi, Universiti Kebangsaan Malaysia

Jalan Raja Muda Abdul Abdul Aziz, 50300 Kuala Lumpur, Malaysia

Received: 3 February 2009 / Accepted: 20 January 2010

ABSTRAK

Penggunaan formulasi tablet pelepasan tertahan untuk dadah anti-inflamatori bukan steroid (DAIBS) seperti aspirin berupaya melindungi lapisan perut dari kesan buruk jus asid tubuh. Kajian ini dilakukan untuk menilai keberkesanan formulasi tablet matriks pelepasan tertahan dengan kepelbagaian kepekatan polimer bersama ketoprofen sebagai model. Tablet dibangunkan dengan menggunakan kaedah granulasi basah yang terdiri daripada polimer hidrofilik (hidroksipropil metilselulosa), polimer hidrifobik bersandar pada pH (Eudragit L100-55) dan polimer tak bersandar pada pH (Eudragit R100) sebagai bahan asas pembentukan matriks pada kepekatan 10%, 20% dan 30%b/b. Semua formulasi dimampatkan dengan menggunakan mesin pentabletan yang mempunyai penebuk berbentuk cembung bersaiz 10 mm. Tablet yang terhasil diuji dari segi keseragaman berat, kekerasan, kerapuhan, ketebalan, % kandungan dadah dan kajian pelepasan in vitro menggunakan kaedah BP 2007. Hasil menunjukkan kadar pelepasan dadah dikawal oleh jenis dan kepekatan polimer di dalam formulasi matriks. Secara umumnya peningkatan kepekatan kandungan polimer di dalam tablet matriks didapati mengurangkan kadar pelepasan dadah. Perbandingan polimer melalui kepekatan yang sama menggunakan t50%, pula mendapati terdapat perbezaan statistik bermakna (P<0.05) pada kadar pelepasan dadah. Berdasarkan kepada pelepasan dadah dalam kajian in vitro, polimer hidrofobik bersandar pada pH (Eudragit L100-55) menunjukkan profil pelepasan dadah secara tertib sifar yang terbaik berbanding polimer yang lain.

Kata kunci: Pelepasan tertahan; tablet matriks; ketoprofen; pelepasan in vitro

ABSTRACT

The use of sustained release tablet formulation for non-steroidal anti-inflammatory drugs (NSAIDs) like aspirin has shown its capability to protect the stomach lining from the adverse effect of gastric juice from the body. This study was carried out to evaluate the efficiency of sustained release matrix tablet formulation using ketoprofen as a model drug with different polymers concentration. The tablets were prepared by the wet granulation method using hydrophilic polymer (hydroxypropyl methylcellulose), hydrophobic pH dependent polymer (Eudragit L100-55) and independent polymer (Eudragit RD 100) as matrix forming retarding materials at 10%w/w, 20%w/w and 30%w/w. All formulations were compressed using 10 mm concave faced punches. The compressed tablets were evaluated for uniformity of weight, friability, hardness, thickness, % drug content and in vitro dissolution test with regard to BP 2007. The results showed that the drug release rate was found to be governed by the type and concentration of polymer in the matrix system. Generally, increasing the polymeric concentration in the matrix tablets will decrease the rate of drug release. When the polymers were compared at similar concentration using t50%, the difference in drug release was found to be statistically significant (p<0.05). Based on the in vitro drug dissolution studies, the hydrophobic pH dependent polymer (Eudragit L100-55) showed a better zero drug release profile compared to other polymers.

Keywords: in vitro dissolution; ketoprofen; matrix tablets; sustained release

REFERENCES

Agrawal, A.M., Neau, S. H. & Bonate, P.L. 2003. Wet granulation fine particle ethylcellulose tablets: Effect of production variables and mathematical modeling of drug release. AAPS PharmSci 5(2): 13.

Alderborn, G. 2002. Tablet & Compaction. Dlm. Pharmaceutics: The science of dosage form design, disunting oleh Aulton, M. hlm. 379-393. London: Churchill Livingstone.

Banker, G. S. 1984. Pharmaceutical application of controlled release: An overview of the past, present and future. Dlm. Medical Application of Controlled Release, Langer, R.S. & Wise, D.L. Boca Raton, FL: CRC Press, Inc.

Bashar M.T. & Tashtoush B.M. 2003. Effect of microenvironment pH of swellable and erodable buffered matrices on the release characteristics of diclofenac sodium. AAPS Pharm. SciTech. 4(3): 43.

BP (British Pharmacopoeia) 2007. CD-Rom Version 11.0.

Chowdary, K. P. R., Mohapatra, P. & Murali Krishna M. N. 2006. Evaluation of olibanum and its resin as controlling matrix for controlled release of diclofenac. Indian J. Pharm. Sci. 68(4): 497-500.

Comoglu, T, Gonul, N. & Baykara, T. 2003. Preparation and in vitro evaluation of modified release ketoprofen microsponges. IL Farmaco 58: 101-106.

Davies N.M. 1999. Sustained Release & Enteric Coated NSAIDs: Are they really GI safe. J. Pharm. Pharmaceut. Sci. 2(1): 5-14.

Dhiman, M., Poddar, S. S. & Shajahan, A. 2003. Development of matrix and coated unit for pH-independent release of a weakly basic drug, (atas talian) http://www.priory.com/pharmol/matrix.htm (5 November 2005).

Foner, D. E., Anderson, N. R. & Banker S. G. 1980. Granulation and tablet characteristics. Dlm. Pharmaceutical dosage forms: Tablet, disunting oleh Lieberman, A. H. & Lachman, L. Jld. 2 hlm. 185-261. New York: Marcel Dekker Inc.

Furlanetto, S., Maestrelli, F., Orlandini, S., Pinzauti, S. & Mura, P. 2003. Optimization of dissolution test precision for a ketoprofen oral extended release product. J. Pharm. Biomed Anal. 32: 159-165.

Giunchedi, P., Gavini, E., Domenico, M., Moretti, L. & Pirisino, G. 2000. Evaluation of Alginate Compressed Matrices as Prolonged Drug Delivery Systems. AAPS J. Pharm. Sci. Tech: 1(3): 19.

Grahnen, A., 1984. Design of bioavailability studies. Int. J. Pharm. 5: 100-103.

Jellin, J. M., Mzrakian, A., Pearson, R. E. & White, J. R. 1999. Ketoprofen. Mosby’s GenRX: The Complete Reference of Generic and Brand Drugs. 9th ed. Missouri. CRC Press, Inc., Louis.

Kamba, M., Seta, Y., Kusai, A. & Nishimura, K. 2001. Evaluation of the mechanical force in stomach of dog. Int. J. Pharm. 228: 209-217.

Khan, M. Z. I., Prebeg, Z, dan Kurjakovic, N. 1999. A pH-dependent colon targeted oral drug delivery system using methacrylic acid copolymers. J. Cont. Rel. 58(1999): 215-222.

Lacy, C. F., Amstrong, L. L., Goldman, M. P. & Lance. 2000. Ketoprofen. Drug Information Handbook. 8th edition. Ohio, United States of America: Lexi-Comp Inc.

Lehmann K. 1996. Practical course in film coating of pharmaceutical dosage forms with Eudragit¨. Pharmaceutical Technology.

Lord, N.G. 1986. Sustained release dosage forms. In The Theory and Practice of Industrial Pharmacy, edited by Lachman, L. Lieberman, H.A. and Kaning, J.L. Philadelphia: Lea & Febiger.

MIMS Annual Malaysia. DIM 2000/2001. Provail CR, Orudis gel, Oruvail. Petaling Jaya: Havas Media.

Odeku, O.A. & Itiola, O.A. 2003. Effects of interacting variables of tensile strength and the release properties of paracetamol tablets. Tropical J. Pharm. Res. 233: 147-198

Omoigui, S. 1995. Ketoprofen. The Pain Drugs Handbook. London: Mosby.

Reddy, K. R., Mutalik, S. & Reddy, S. 2003. One daily sustained release matrix tablets of ncorandil: formulation and in vitro evaluation. AAPS Pharm Sci Tech 2003: 2003. Comparative evaluation of plastic, hydrophobic and hydrophilic polymers as matrices for controlled release drug delivery. J. Pharm. Sci. 6(2): 274-291.

Roda, A., Sabatini, L, Mirasoli, M., Baraldini, M. & Roda, E. 2002. Bioavailability of a new ketoprofen formulation for once daily oral administration. Int. J. Pharm. 241: 165-172.

Rudnic, E.M., Schwartz, D.J. 2000. Oral solid dosage form. Dlm. A.R. (pnyt). Remington: The science and practice of pharmacy. 20th ed. United state of America: Lippincott Williams & Wilkins.

Silvina, A., Bravo, Maria, C., Lamas & Cloudio J. Salomon. 2002. In vitro studies of diclofenac sodium controlled release from biopolymeric hydrophilic matrices. J. Pharm. Sci. 5(3): 213-219.

Solinis, M.A, Cruz, Y., Hernandez, R. M, Gascon, A. R, Calvo, B. & Pedraz, J. L. 2002. Release of ketoprofen enantiomers from HPMC K100M matrices-diffusion studies. Int. J. Pharm. 239: 61-68.

Vasant, V., Ranade, Mannfred A. & Hollinger 2004. Drug Delivery System. Second Edition. CRC Press, Inc, Pharmacology & Toxicology Series.

Yeole, P. G., Galgatte, U. C., Babla, I. B. & Nakhat, P.D. 2006. Design and evaluation of xanthan gum-based sustained matrix tablets of diclofenac sodium. Indian J. Pharm. Sci. 68(2): 185-189.

*Corresponding author; email: mciamin@pharmacy.ukm.my