Effect of Hydrophilic Polymers on the Release Rate and Pharmacokinetics of Acyclovir Tablets Obtained by Wet Granulation: In Vitro and In Vivo Assays
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 comb...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/19/6490 |
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| author | D. Nagasamy Venkatesh Subramanianainar N. Meyyanathan Andjelka Kovacevic Aleksandra Zielińska Joel Fonseca Piotr Eder Agnieszka Dobrowolska Eliana B. Souto |
| author_facet | D. Nagasamy Venkatesh Subramanianainar N. Meyyanathan Andjelka Kovacevic Aleksandra Zielińska Joel Fonseca Piotr Eder Agnieszka Dobrowolska Eliana B. Souto |
| author_sort | D. Nagasamy Venkatesh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T21:24:28Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T21:24:28Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3b01f163acfa4806846a2033d77fc9a22023-11-23T21:12:15ZengMDPI AGMolecules1420-30492022-10-012719649010.3390/molecules27196490Effect of Hydrophilic Polymers on the Release Rate and Pharmacokinetics of Acyclovir Tablets Obtained by Wet Granulation: In Vitro and In Vivo AssaysD. Nagasamy Venkatesh0Subramanianainar N. Meyyanathan1Andjelka Kovacevic2Aleksandra Zielińska3Joel Fonseca4Piotr Eder5Agnieszka Dobrowolska6Eliana B. Souto7Department 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, IndiaDepartment 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, IndiaDepartment of Pharmaceutical Technology, Institute of Pharmacy, Friedrich-Schiller University Jena, Helmholtzweg 4, 07743 Jena, GermanyInstitute of Human Genetics, Polish Academy of Sciences, Strzeszyńska 32, 60-479 Poznan, PolandDepartment of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira, 228, 4050-313 Porto, PortugalDepartment of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, PolandDepartment of Gastroenterology, Dietetics and Internal Diseases, Poznan University of Medical Sciences, 60-355 Poznan, PolandDepartment of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira, 228, 4050-313 Porto, PortugalThis 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.https://www.mdpi.com/1420-3049/27/19/6490acyclovirhydrophilic polymerssustained release profilepharmacokineticsin vitro and in vivo testing |
| spellingShingle | D. Nagasamy Venkatesh Subramanianainar N. Meyyanathan Andjelka Kovacevic Aleksandra Zielińska Joel Fonseca Piotr Eder Agnieszka Dobrowolska Eliana B. Souto Effect of Hydrophilic Polymers on the Release Rate and Pharmacokinetics of Acyclovir Tablets Obtained by Wet Granulation: In Vitro and In Vivo Assays Molecules acyclovir hydrophilic polymers sustained release profile pharmacokinetics in vitro and in vivo testing |
| title | Effect of Hydrophilic Polymers on the Release Rate and Pharmacokinetics of Acyclovir Tablets Obtained by Wet Granulation: In Vitro and In Vivo Assays |
| title_full | Effect of Hydrophilic Polymers on the Release Rate and Pharmacokinetics of Acyclovir Tablets Obtained by Wet Granulation: In Vitro and In Vivo Assays |
| title_fullStr | Effect of Hydrophilic Polymers on the Release Rate and Pharmacokinetics of Acyclovir Tablets Obtained by Wet Granulation: In Vitro and In Vivo Assays |
| title_full_unstemmed | Effect of Hydrophilic Polymers on the Release Rate and Pharmacokinetics of Acyclovir Tablets Obtained by Wet Granulation: In Vitro and In Vivo Assays |
| title_short | Effect of Hydrophilic Polymers on the Release Rate and Pharmacokinetics of Acyclovir Tablets Obtained by Wet Granulation: In Vitro and In Vivo Assays |
| title_sort | effect of hydrophilic polymers on the release rate and pharmacokinetics of acyclovir tablets obtained by wet granulation in vitro and in vivo assays |
| topic | acyclovir hydrophilic polymers sustained release profile pharmacokinetics in vitro and in vivo testing |
| url | https://www.mdpi.com/1420-3049/27/19/6490 |
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