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Effect of Hydrophilic Polymers on the Release Rate and Pharmacokinetics of Acyclovir Tablets Obtained by Wet Granulation: In Vitro and In Vivo Assays

ORCID
0000-0001-9347-0228
Affiliation
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Rocklands, Post Box. No. 20, Elk Hill Road, The Nilgiris, Ooty 643001, Tamil Nadu, India
Venkatesh, D. Nagasamy;
Affiliation
Department of Pharmaceutical Analysis, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Rocklands, Post Box. No. 20, Elk Hill Road, The Nilgiris, Ooty 643001, Tamil Nadu, India
Meyyanathan, Subramanianainar N.;
Affiliation
Department of Pharmaceutical Technology, Institute of Pharmacy, Friedrich-Schiller University Jena, Helmholtzweg 4, 07743 Jena, Germany
Kovacevic, Andjelka;
ORCID
0000-0003-2603-1377
Affiliation
Institute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznan, Poland
Zielińska, Aleksandra;
Affiliation
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Fonseca, Joel;
ORCID
0000-0001-9306-5038
Affiliation
Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, Poland
Eder, Piotr;
ORCID
0000-0002-3647-5070
Affiliation
Department of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, Poland
Dobrowolska, Agnieszka;
ORCID
0000-0002-9737-6017
Affiliation
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Souto, Eliana B.

This study aims to evaluate the feasibility of producing acyclovir-containing modified release matrix tablets by a wet granulation method based on the type and concentration of two pharmaceutical-grade hydrophilic matrix polymers (i.e., hydroxypropyl methylcellulose (HPMC), carbomers, and their combinations) commonly used in biomedical applications. The mechanical properties of the tablets and in vitro and in vivo performance were studied. The physicochemical properties of the raw materials and corresponding physical mixtures were characterized by differential scanning calorimetry, showing that the hydrophilic polymers did not influence the physicochemical properties of the drug. The wet granulation process improved the flow and compression properties of the obtained granules. This method enabled the preparation of the matrix tablets of acyclovir with appropriate mechanical properties concerning hardness and friability. The drug release kinetics was governed by the type and concentration of the hydrophilic polymers composing the matrices. The study has proven that HPMC-composed tablets were superior in modified drug release properties compared to carbomer- and HPMC/carbomer-based tablets. Mathematical analysis of the release profiles, determined in a medium adjusted to pH 1.2 followed by pH 7.4, revealed that the drug released from the hydrophilic tablets followed non-Fickian first-order kinetics. An optimal HPMC-based formulation submitted to accelerated stability studies (40 °C, 75% RH) was stable for three months. A complete cross-over bioavailability study of the selected acyclovir-loaded sustained release tablets and marketed immediate-release tablets were compared in six healthy male volunteers. The extent of drug absorption from the sustained release tablets was significantly greater than that from immediate-release pills, which may improve the drug’s antiviral properties attributed to the lower elimination rate and enhanced acyclovir half-life.

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