FORMULATION A CIPROFLOXACIN HYDROCHLORIDE EXTENDED-RELEASE TABLET WITH COMBINATION OF HYDROXYPROPYL METHYLCELLULOSE (HPMC) K100M AND HYDROXYPROPYL METHYLCELLULOSE (HPMC) K4M BY DIRECT COMPRESSION METHOD

Authors

  • RESMI MUSTARICHIE Faculty of Pharmacy, Universitas Padjadjaran, Hegarmanah, Jatinangor, Kabupaten Sumedang, Jawa Barat 45363, Indonesia
  • DOLIH GOZALI Faculty of Pharmacy, Universitas Padjadjaran, Hegarmanah, Jatinangor, Kabupaten Sumedang, Jawa Barat 45363, Indonesia
  • YEDI HERDIANA Faculty of Pharmacy, Universitas Padjadjaran, Hegarmanah, Jatinangor, Kabupaten Sumedang, Jawa Barat 45363, Indonesia

DOI:

https://doi.org/10.22159/ijap.2020v12i1.35522

Keywords:

Ciprofloxacin hydrochloride, Extended-release, Direct compression, In process control, Dissolution test

Abstract

Objective: Ciprofloxacin hydrochloride tablets which are not extended-release will produce non-constant drug levels in the blood. This study aimed to overcome this problem by making ciprofloxacin hydrochloride extended-release tablets with a combination of hydroxypropyl methylcellulose (HPMC) K100M and hydroxypropyl methylcellulose (HPMC) K4M by a direct compression method.

Methods: The method in this study consisted of preformulation, formula design, manufacture of ciprofloxacin hydrochloride tablets, tablet print mass testing, IPC (In-Process Control) slow-release tablet mass print, IPC (In-Process Control) quality of slow-release tablet preparation, dissolution test, and statistical analysis. Preformulation was carried out aiming to determine the physical and chemical properties of active-excipient substances based on a certificate of analysis. This was done using a Fourier Transform Infrared (FT-IR) and UV-Vis spectrophotometer. Five kinds of ciprofloxacin hydrochloride tablet formulations were made using the direct pressing method with variations in the concentration of HPMC K100M and HPMC K4M. The ratio of percentage of HPMC K100M and HPMC K4M were F1 0,5%: 1%, F2 1%: 0,5%, F3 0,75%: 0,75%, F4 1%: 0%, F5 0%: 3%. Evaluation of tablet preparations (IPC control) included weight uniformity test, size uniformity test, hardness test, and friability test. The dissolution test was carried out for 2 h by hydrochloride acid 0,1 N pH 1.2 as (pH of gastric acid). Statistical analysis using Perfect Block Random Design (PBRD) method and further testing using the Newman-Keuls test was applied for the data obtained.

Results: The test results with FTIR showed that ciprofloxacin hydrochloride used compared to ciprofloxacin hydrochloride BPFI is equivalent and has a purity index of 0.992739. Determination of the level of the active ingredient ciprofloxacin hydrochloride was carried out by measuring the absorbance of a 5 ppm sample solution at a wavelength of 276 nm. The percentage of absorbance of the solution is then calculated and the result obtained is 98.87%. The range of levels that have been set is 98%-102%. These test results were under those listed on the certificate of analysis. The results of the IPC test in the form of weight uniformity test, size uniformity test, hardness test, friability test, and uniformity of ciprofloxacin hydrochloride levels in the preparation, showed all data obtained fulfilling the requirements set by USP 36 convention (2013). The result from dissolution tablet test on 30, 60, and 120 min showed the release of active substance on F1 56.00 %, 67.76 %, and 87.57 %. F2 were 53.42 %, 65.16 %, and 91.44 %. F3 were 59.18 %, 72.15 %, and 91.20 %. F4 were 50.51 %, 70.70 %, and 95.29 %. F5 were 53.75 %, 69.55 %, and 92.05 %. Statistical analysis was applied for the data obtained. Dissolution results illustrated the level of active substances dissolved in the dissolution medium for 2 h or in other words the dissolution test results indicated the number of active substances from tablets that were released and enter the digestive tract and came in contact with body fluids.

Conclusion: The dissolution test results as a basis of extended-release tablets showed all of the formulae met dissolution requirements of the United States Pharmacopeia (USP) 36 convention.

Downloads

Download data is not yet available.

References

Coleman MD. Human drug metabolism: an introduction. John Wiley and Sons; 2010. p. 1-9.

Indrawati T. New oral drug delivery system with controlled release (Indonesian: sistem penghantaran obat baru per oral dengan pelepasan terkontrol). Sainstech Pharma 2011;2:1-7.

Arayne MS, Hussain F, Sultana N. Interactions between ciprofloxacin and antacids-dissolution and adsorption studies. Drug Metab Drug Interact 2005;21:117-29.

Babar S. SIADH associated with ciprofloxacin. Ann Pharmacother 2013;47:1359–63.

Schuetz AN. Antimicrobial resistance and susceptibility testing of anaerobic bacteria. Clin Infect Dis 2014;59:698–705.

Prasad RR, Shree V, Kumar R, Kala K, Kumar P. Prevalence and antibiotic sensitivity of pseudomonas aeruginosaisolated from CSOM in NMCH, Patna, India. Int J Curr Microbiol Appl Sci 2017;6:2912-6.

Orazi G, Ruoff KL, O'Toole GA. Pseudomonas aerugino-saincreases the sensitivity of biofilm-grown staphylococcusaureusto membrane-targeting antiseptics and antibiotics. mBio 2019;10:e01501-19.

Ali SQ, Zehra A, Naqvi BS, Shah S, Bushra R. Resistance pattern of ciprofloxacin against different pathogens. Oman Med J 2010;25:294–8.

Iype MSM, Kunoor A, Anila KN. A treatment dilemma concerning immunosuppressant use: a case report. Asian J Pharm Clin Res 2017;10:4-6.

Soebandrio AR, Setiabudi S, dan Widodo D. The use of ciprofloxacin in Indonesia, Jakarta: Departemen Kesehatan Republik Indonesia; 2005.

Ansel HC. Introduction to pharmacy dosage forms (Indonesian: Pengantar Bentuk Sediaan Farmasi) Edisi Keempat. Penerjemah: Farida Ibrahim. Jakarta: Penerbit Universitas Indonesia; 2005. p. 162-3, 357-89.

Lachman L, Lieberman HA, Kanig JL. The theory and practice of industrial pharmacy. 3rd Edition. Philadelphia: Lea and Febiger; 1990. p. 293-345.

Siregar C. Pharmaceutical technology tablets preparation of practical basics (Indonesian: Teknologi Farmasi Sediaan Tablet Dasar-Dasar Praktis), Jakarta: EGC; 2010. p. 120-5.

Rowe RC, Sheskey PJ, Quinn ME. American pharmacists association. Handbook of Pharmaceutical Excipients. 6th Edition. Washington DC and London: American Pharmacist Association and Pharmaceutical Press; 2009.

Bhattacharya SA. Formulation and evaluation of ciprofloxacin controlled release matrix tablets introduction. Int J Pharm Res Allied Sci 2012;1:1-7.

Kumar KA, Tandrima M, Subhabrota M, Beduin M, Banhishikha K, Satyam C, et al. Design, formulation, and evaluation of sustained-release bilayer tablets of ciprofloxacin hydrochloride. J Drug Delivery Ther 2019;9:46-53.

Pandey S, Pandey P, Tiwari G, Tiwari R, Rai AK. FTIR spectroscopy: a tool for quantitative analysis of ciprofloxacin in tablets. Indian J Pharm Sci 2012;74:86–90.

Al-Omar MA. Ciprofloxacin: physical profile. Profiles Drug Subst Excipients Relat Methodol 2005;31:163-78.

Mukti AA, Jannah F, Nurrochmad A, Lukitaningsih E. Development and validation method for the quantitative determination of ciprofloxacin in human plasma and its application in bioequivalence test. Asian J Pharm Clin Res 2016;9:89-95.

The United States Pharmacopeia. The National Formulary 22. 27th Edition. Washington DC: United States Pharmacopeia Convention Inc; 2004.

The United States Pharmacopeia. The National Formulary 23. 29th Edition. Volume I. Washington DC: United States Pharmacopeia Convention Inc;2006.

The United States Pharmacopeia Convention. The National Formulary 31. 36th Edition. Volume I. Washington DC: United States Pharmacopeia Convention Inc; 2013.

Aulton ME. Pharmaceutics the science of dosage form design. New York: Churchill Livingstone; 2002. p. 02, 124, 246-48.

Fahmy S, Abu Gharbieh E. In vitro dissolution and in vivo bioavailability of six brands of ciprofloxacin tablets administered in rabbits and their pharmacokinetic modeling. J Biomed Biotechnol 2014;4:1-8.

Sahoo S, Chakraborti CK, Mishra SC. Qualitative analysis of controlled release ciprofloxacin/carbopol 934 mucoadhesive suspension. J Adv Pharm Technol Res 2011;2:195–204.

Departemen Kesehatan Republik Indonesia. Farmakope Indonesia. Edisi IV. Jakarta: Departemen Kesehatan Republik Indonesia; 1995.

Malodia K, Kumar A, Kumar S, Rakha P. Formulation and evaluation of extended-release tablets of salbutamol sulfate. Der Pharm Lett 2013;5:177-81.

United States Pharmacopeial Convention Usp. Usp36-Nf31. Vol. 1; 2012.

Rowe RC, Sheskey PJ, Quinn ME. Handbook of pharmaceutical excipients. 6th Edition. Washington DC and London: American Pharmacist Association and Pharmaceutical Press; 2009. p. 115-118, 311-322.

Tadey T, Carr G. Dissolution testing for solid oral dosage forms. Pharm Formulation Quality 2009;11:22-7.

Beyssac E, Lavigne J. Dissolution study of active pharmaceutical ingredients using the flow through apparatus usp 4, dissolution technologies; 2005. p. 23-5.

Yunitasari EW. Design and analysis of experiments using a completely random block in the case of missing data in PT. A B C (Indonesian: Desain dan analisis eksperimen menggunakan blok lengkap acak pada kasus data hilang di PT. ABC). IEJST 2018;2:27-34.

Sudjana S. Experimental design and analysis (Indonesian: Desain Dan Analisis Eksperimen), Edisi keempat, Bandung: Penerbit PT. Tarsito; 1995.

Abdi H, Williams LJ. Newman-keuls test and tukey test. Available from: https://www.researchgate.net/publication/ 242146550.

Published

15-01-2020

How to Cite

MUSTARICHIE, R., GOZALI, D., & HERDIANA, Y. (2020). FORMULATION A CIPROFLOXACIN HYDROCHLORIDE EXTENDED-RELEASE TABLET WITH COMBINATION OF HYDROXYPROPYL METHYLCELLULOSE (HPMC) K100M AND HYDROXYPROPYL METHYLCELLULOSE (HPMC) K4M BY DIRECT COMPRESSION METHOD. International Journal of Applied Pharmaceutics, 12(1), 25–30. https://doi.org/10.22159/ijap.2020v12i1.35522

Issue

Section

Original Article(s)