OPTIMIZATION OF ACYCLOVIR SUSPENSION: FORMULATING DEVELOPMENT USING NA-CMC AND QUALITY CONTROL OF FINISHED PRODUCTS

RESMI MUSTARICHIE; DRAJAD PRIAMBODO; DANNI RAMDHANI; NYI MEKAR SAPTARINI

doi:10.22159/ijap.2022.v14s5.28

Authors

RESMI MUSTARICHIE Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, West Java, Indonesia
DRAJAD PRIAMBODO Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, West Java, Indonesia
DANNI RAMDHANI Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, West Java, Indonesia
NYI MEKAR SAPTARINI Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, West Java, Indonesia

DOI:

https://doi.org/10.22159/ijap.2022.v14s5.28

Keywords:

Acyclovir, Suspension, Formulation, Quality control, Na-CMC, Spectrophotometer UV-Vis

Abstract

Objective: Acyclovir is widely used as a potent antiviral drug to treat viral infections of herpes and varicella-zoster families. Unfortunately, the drug has a very poor oral bioavailability character (15-30%). The purpose of this study was to develop a formulation of acyclovir suspension with a simple suspension method using Na-CMC (carboxymethylcellulose sodium), and to carry out quality control of the finished product.

Methods: The formulation was developed by designing variations in Na-CMC concentration and quality control, including pH, viscosity, dispersibility, storage stability, microscopic measurement, sedimentation volume, and evaluation of acyclovir levels. Quality control is to evaluate the suspension in order to obtain good and stable physicochemical properties of the suspension.

Results: Design variations of Na-CMC concentrations of 1.4%, 1.5%, and 1.6% resulted in a homogeneous suspension and easily dispersed perfectly. The three formulas did not have a significant difference in the value of viscosity, permeability, and sedimentation volume, which were not significant. All formulas have pseudoplastic flow properties, with good particle size uniformity in the range of 0–13 µm. The stability of pH during storage time was shown by the formula with 1.5% Na-CMC.

Conclusion: The acyclovir suspension with 1.5% Na-CMC concentration was the best compared to the other formulas in terms of stability and physicochemical properties.

Downloads

Download data is not yet available.

References

Balfour HH. Current management of varicella-zoster virus infections. J Med Virol. 1993;Suppl(1):74-81. doi: 10.1002/jmv.1890410514, PMID 8245897.

Patel D, Sawant KK. Oral bioavailability enhancement of acyclovir by self-micro emulsifying drug delivery systems (SMEDDS). Drug Dev Ind Pharm. 2007;33(12):1318-26. doi: 10.1080/03639040701385527, PMID 18097805.

Sachan NK, Pushkar S, Solanki SS, Bhatere DS. Enhancement of solubility of acyclovir by solid dispersion and inclusion complexation methods. W Appl Sci J. 2010;11(7):857-64.

Wagstaff AJ, Faulds D, Goa KL. Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1994;47(1):153-205. doi: 10.2165/00003495-199447010-00009, PMID 7510619.

Reardon JE, Spector T. Acyclovir: mechanism of antiviral action and potentiation by ribonucleotide reductase inhibitors. Adv Pharmacol. 1991;22:1-27. doi: 10.1016/s1054-3589(08)60031-9, PMID 1958500.

O’Brien JJ, Campoli Richards DM. Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1989;37(3):233-309. doi: 10.2165/00003495-198937030-00002, PMID 2653790.

Aulton ME. Aulton’s pharmaceutics: the design and manufacture of medicines. 3rd ed. Edinburgh: Churchill Livingstone Elsevier; 2007.

Mahato RI, Narang AS. Pharmaceutical dosage forms and drug delivery. 2nd ed. Boca Raton, FL: CRC Press; 2012.

Ash M, Ash I, Knovel. Handbook of fillers, extenders, and diluents [electronic resource]. 2nd ed Endicott NY, editor Synapse Information Resources. Vol. XV; 2008. p. 1029.

Jannin V, Lemagnen G, Gueroult P, Larrouture D, Tuleu C. Rectal route in the 21st Century to treat children. Adv Drug Deliv Rev. 2014;73:34-49. doi: 10.1016/j.addr.2014.05.012, PMID 24871671.

Yadav MS, dhole, P Chavan. Nanosuspension: a novel techniques in drug delivery system. World J Pharm Pharm Sci. 2014;3(2):410-33.

Behra JS, Mattsson J, Cayre OJ, Robles ESJ, Tang H, Hunter TN. Characterization of sodium carboxymethyl cellulose aqueous solutions to support complex product formulation: A rheology and light scattering study. ACS Appl Polym Mater. 2019;1(3):344-58. doi: 10.1021/acsapm.8b00110.

Ministry of Health Republic of Indonesia. Farmakope Indonesia. 4th ed. Jakarta: Ministry of Health Republic of Indonesi; 1995. p. 65.

British pharmacopeia. Vol. I. London: Health Ministers of the United Kingdom; 2018.

United States pharmacopeial C. The United States pharmacopeia: the national formulary. Rockville, Md: United States pharmacopeial convention; 2006.

Volpato NM, Santi P, Laureri C, Colombo P. Assay of acyclovir in human skin layers by high-performance liquid chromatography. J Pharm Biomed Anal. 1997;16(3):515-20. doi: 10.1016/s0731-7085(97)00091-5, PMID 9589411.

Arnal J, Gonzalez Alvarez I, Bermejo M, Amidon GL, Junginger HE, Kopp S. Biowaiver monographs for immediate release solid oral dosage forms: aciclovir. J Pharm Sci. 2008;97(12):5061-73. doi: 10.1002/jps.21392, PMID 18425814.

Cortesi R, Esposito E. Acyclovir delivery systems. Expert Opin Drug Deliv. 2008;5(11):1217-30. doi: 10.1517/17425240802450340, PMID 18976132.

Abedian B, Kachanov M. On the effective viscosity of suspensions. Int J Eng Sci. 2010;48(11):962-5. doi: 10.1016/j.ijengsci.2010.08.012.

Ibroma SD, Cookey GA, Obunwo CC. Effect of carboxymethylcellulose biopolymer on sedimentation properties of trimagnesium, tricalcium and Tristrontiu phosphates precipitates. J Appl Sci Environ Manag. 2018;22(10):1591-94.

Khaled B, Abdelbaki B. Rheological and electrokinetic properties of carboxymethylcellulose water dispersions in the presence of salts. Int J Phys Sci. 2012;7(11):1790-8.

Benchabane A, Bekkour K. Rheological properties of carboxymethyl cellulose (CMC) solutions. Colloid Polym Sci. 2008;286(10):1173-80. doi: 10.1007/s00396-008-1882-2.

Rahman MS, Hasan MS, Nitai AS, Nam S, Karmakar AK, Ahsan MS. Recent developments of carboxymethyl cellulose. Polymers. 2021;13(8):1345. doi: 10.3390/polym13081345, PMID 33924089.

Darshana P, Madhavi P, Ravi G, Anamik S, Ranjan K. UV-vis spectrophotometric assay determination of oral antiplatelet ticafrelor drug in pharmaceutical formulation: application to content uniformity. J Chem Pharm Res. 2016;8(1):316-21.

Hintz RJ, Johnson KC. The effect of particle size distribution on dissolution rate and oral absorption. Int J Pharm. 1989;51(1):9-17. doi: 10.1016/0378-5173(89)90069-0.