Optimization Matrix Formulas Using Hypromellose and Carboxymethylcellulose Sodium for Metformin HCl Extended Release Caplets

Agus Andrie, Insan Sunan Kurniawan Syah, Anis Yohana Chaerunisaa

Abstract

The first-line pharmacological therapy in type II diabetes patients in people who are overweight and have normal kidney function is metformin. However, metformin with immediate release has been found to have some weaknesses, namely that a maximum dose of 2,000 mg/day requires use 2 to 3 times a day, which leads to a potential patient's non-compliance, in addition to causing disorders in the intestinal tract. To overcome this problem, a formulation was developed that was modified with extended release using the direct compressed method. This study aims to determine the influence of variations in the concentration of hypromellose and carboxymethylcellulose natrium (Na-CMC) matrices in the extended-release of metformin HCl 500 mg to obtain an optimal and similar extended-release system capsule formula to the originator drug, as well as to prove the quality of the selected formula through stability monitoring. This research is expected to produce the optimum formula for metformin HCl capsules extended release and can be applied in the pharmaceutical industry into commercial products.

Keywords: Diabetes, Metformin HCl, Extended release, Direct compressed,
                    Hypromellose, Carboxymethylcellulose natrium.

Full Text:

PDF

References

World Health Organization. Classification of Diabetes Mellitus 2019. World Health Organization, editor. Switzerland: World Health Organization; 2019. 2–29.

Tandra H. Segala Sesuatu yang Harus Anda Ketahui Tentang Diabetes Panduan Lengkap Mengenal dan Mengatasi Diabetes dengan Cepat dan Mudah. Edisi Kedua. Jakarta: PT Gramedia Pustaka Utama; 2018. 1–289.

American Diabetes Association. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes 2020. Diabetes Care. 2020;43: S14–31.

Handorf A, Hans W, Tausif A. Insulin Gene Therapy for Type 1 Diabetes Mellitus. Experimental and Clinical Transplantation. 2015;13(1):3745.

Roy H, Chandan K, Sisir N, Kirti R. Formulation and Design of Sustained Release Matrix Kaplets of Metformin Hydrochloride: Influence of Hypromellose and Polyacrylate Polymers. Int J Appl Basic Med Res. 2013;3(1):55.

Cetin M, Selma S. Microparticulate and Nanoparticulate Drug Delivery Systems for Metformin Hydrochloride. Drug Deliv. 2016;23(8):2796–805.

Hameed M, Khurshid K, Sadia S, Nasir M. Dose Comparison and Side Effect Profile of Metformin Extended Release Versus Metformin Immediate Release. J Ayub Med Coll Abbottabad [Internet]. 2017;29(2):225–9.

Nayak A, Dilipkumar P, Kousik S. Swelling and Drug Release Behavior of Metformin Hcl-Loaded Tamarind Seed Polysaccharide-Alginate Beads. Int J Biol Macromol. 2016; 82:1023–7.

Tan J, Wang Y, Liu S, Shi Q, Zhou X, Zhou Y, et al. Long-Acting Metformin Vs. Metformin Immediate Release in Patients with Type 2 Diabetes: A Systematic Review. Front Pharmacol. 2021;12(669814):1–9.

Alam K, Farya Z, Huma S. Development and Evaluation of Metformin Hydrochloride 500 mg Sustained Release Tablets. J Pharm Biomed Sci. 2013;36(36):1844–52.

Vaingankar P, Purnima A. Continuous Melt Granulation to Develop High Drug Loaded Sustained Release Tablet of Metformin HCl. Asian J Pharm Sci. 2017;12(1):37–50.

Haque S, Sheela A. Development of Polymer-bound Fast-dissolving Metformin Buccal Film with Disintegrants. Int J Nanomedicine. 2015;10(1):199–205.

Abrilla A, A Nico N, Cecilia A. Metformin Extended-release Versus Metformin Immediate-release For Adults with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Diabetes Res Clin Pract. 2021;178(108824).

Ofori-Kwakye K, Kwadwo A, Samuel L, Noble K, Mariam E. Development and Evaluation of Natural Gum-based Extended-Release Matrix Tablets of Two Model Drugs of Different Water Solubilities by Direct Compression. Saudi Pharmaceutical Journal. 2016;24(1):82–91.

Baker C, Cimmaron R, Vatsala S, Renee P, Victoria A, Neda R. Should Metformin Remain the First-Line Therapy for Treatment of Type 2 Diabetes? Ther Adv Endocrinol Metab. 2021;12.

Kakad S, Rachh P. Effect of Hydrophilic Polymer and Binder on Drug Release of Metformin HCl Sustained Release Tablet. Int J Health Sci (Qassim). 2022;6(3):6625–3343.

Kang J, Chun M, Cho M, Kwon Y, Choi J, Kim D, et al. Preparation and Characterization of Metformin Hydrochloride Controlled-Release Tablet Using Fatty Acid Coated Granules. Drug Dev Ind Pharm. 2020;46(5):852–60.

Oh J, Ji Eun L, Yu Jeong K, Tack-Oon O, SungKyun H, Eun Kyung K, et al. Designing of the Fixed-Dose Gastroretentive Bilayer Tablet for Sustained Release of Metformin and Immediate Release of Atorvastatin. Drug Dev Ind Pharm. 2016;42(2):340–9.

Abebe A, Ilgaz A, Omar S, Niranjan K, Alberto M. Review of Bilayer Tablet Technology. Int J Pharm. 2014 Jan 30;461(1–2):549–58.

Qin C, Wei H, Chunli Z, Mengmeng W, Zhu J, Qiang Z, et al. Controlled Release of Metformin Hydrochloride and Repaglinide from Sandwiched Osmotic Pump Tablet. Int J Pharm. 2014;466(1–2):276–85.

Momoh M, F.C. Kenechukwu, A. A. Attama. Formulation and Evaluation of Novel Solid Lipid Microparticles as a Sustained Release System for The Delivery of Metformin Hydrochloride. Drug Deliv. 2013;20(3–4):102–11.

Tungadi. Teknologi Sediaan Solida. Ponorogo: Wade Group; 2018.

Obara S. Comparison Between Direct Compression and Wet Granulation Method in The Preparation of Hydrophilic Matrix Tablets Using Hypromellose (HPMC). Journal of Pharmacy and Pharmacology. 2006;76.

Zaman N, Iyan S. Metoda Pembuatan dan Kerusakan Fisik Sediaan Kaplet. Majalah Farmasetika. 2020;5(2):82–93.

Fukui S, Hideki Y, Shuichi Y, Tsuyoshi M, Hidemi M. Design and Evaluation of an Extended-Release Matrix Tablet Formulation; The Combination of Hypromellose Acetate Succinate and Hydroxypropylcellulose. Asian J Pharm Sci. 2017;12(2):149–56.

Collect J, Moreton C. Modified Release Per Oral Dosage Form’.in Aulton, M.E, (ed). Pharmaceutics The Science of Dosage Form Design. 2nd Edition. Edinburg: Churchill Livingstone; 2006. 483–494.

Sukbhir L, Ram K. Formulation and Development of Sustained Release Matrix Kaplets containing Metformin Hydrochloride. Pharmacologyonline. 2011; 2:879–85.

Timmins P, Samuel R, Colin D. Hydrophilic Matrix Tablets for Oral Controlled Release. Advances in the Pharmaceutical Sciences Series. 2014;16(3):53–85.

Pharmacopeia USP. The United States Pharmacopeia, USP 44/The National Formulary, NF 39. Rockville: U.S. Pharmacopeial Convention, Inc.; 2021.

Voight R. Buku Pelajaran Teknologi Farmasi, Diterjemahkan oleh Soendari Noerono. Yogyakarta: Gajah Mada University Press; 1995. 566–567.

Hati M, Yandi S, Bambang H. Pengaruh Kombinasi Matriks terhadap Karakter Tablet Metformin HCl Lepas Lambat Sistem Floating Effervescent. Pharmaceutical Journal of Indonesia. 2022;7(2):89–96.

Carson J, Pittenger B. Bulk Properties of Powders, ASM Handbook: Powder Metal Technologies and Applications. USA: ASM International; 2013.

Garg G, S. S. Mallick, Pablo G, R. J. Berry. An Investigation into The Flowability of Fine Powders Used in Pharmaceutical Industries. Powder Technology. 2018; 336:375–82.

Tan G, David A, Ian L. On The Methods to Measure Powder Flow. Current Pharmaceutical Design. 2015;21(40): 5751–65.

Moghbel A, Hamideh A. Study of Compressibility Properties of Yogurt Powder in Order to Prepare a Complementary Formulation. Iranian Journal of Pharmaceutical Research. 2013;12(3):231–7.

Moravkar K, Tariq M, Jaywant N, Purnima D. Application of Moisture Activated Dry Granulation (MADG) Process to Develop High Dose Immediate Release (IR) Formulations. Advanced Powder Technology. 2017;28(4):1270–80.

Allen L, Ansel H. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Journal of Chemical Information and Modeling. 2014;53(9):1–809.

Depkes RI. Farmakope Indonesia Edisi V. Jakarta: Departemen Kesehatan Republik Indonesia; 2014.

Izzati N, Nuwarda R. Variasi Metode Uji Disolusi Terbanding (UDT). Farmaka Suplemen. 2017;15(1):29–38.

BPOM RI. Peraturan Badan Pengawas Obat dan Makanan Nomor 14 Tahun 2019 Tentang Penarikan dan Pemusnahan Obat Yang Tidak Memenuhi Standar dan/atau Persyaratan Keamanan, Khasiat, Mutu, dan Label. In Jakarta, Jakarta: BPOM RI; 2019.

Peraturan Kepala Badan Pengawas Obat dan Makanan. Peraturan Kepala Badan Pengawas Obat dan Makanan. Peraturan Kepala Badan Pengawas Obat dan Makanan Republik Indonesia Nomor HK.03.1.23.12.11.10217 Tahun 2011 Tentang Obat Wajib Uji Ekivalensi Jakarta; 2011.

Nurmiah S, Syarief R, Sukarno S, Peranginangin R. Aplikasi Response Surface Methodology Pada Optimalisasi Kondisi Proses Pengolahan Alkali Treated Cottonii (ATC). Jurnal Pascapanen dan Bioteknologi Kelautan dan Perikanan. 2013;8(1):9–22.

DOI: https://doi.org/10.24198/idjp.v5i3.53135

Refbacks

  • There are currently no refbacks.