PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11955809

Didanosine extended-release matrix tablets: optimization of formulation variables using statistical experimental design.

Carla Sánchez-Lafuente·Sandra Furlanetto·Mercedes Fernández-Arévalo·Josefa Alvarez-Fuentes·Antonio M Rabasco·M Teresa Faucci·Sergio Pinzauti·Paola Mura
View original source ↗Export metadata ↓

Abstract

Statistical experimental design was applied to evaluate the influence of some process and formulation variables and possible interactions among such variables, on didanosine release from directly-compressed matrix tablets based on blends of two insoluble polymers, Eudragit RS-PM and Ethocel 100, with the final goal of drug release behavior optimization. The considered responses were the percent of drug released at three determined times, the dissolution efficiency at 6 h and the time to dissolve 10% of drug. Four independent variables were considered: tablet compression force, ratio between the polymers and their particle size, and drug content. The preliminary screening step, carried out by means of a 12-run asymmetric screening matrix according to a D-optimal design strategy, allowed evaluation of the effects of different levels of each variable. The drug content and the polymers ratio had the most important effect on drug release, which, moreover, was favored by greater polymers particle size; on the contrary the compression force did not have a significant effect. The Doehlert design was then applied for a response-surface study, in order to study in depth the effects of the most important variables. The desirability function was used to simultaneously optimize the five considered responses, each having a different target. This procedure allowed selection, in the studied experimental domain, of the best formulation conditions to optimize drug release rate. The experimental values obtained from the optimized formulation highly agreed with the predicted values. The results demonstrated the reliability of the model in the preparation of extended-release matrix tablets with predictable drug release profiles.

Explore related subjects

Anti-HIV AgentsChemistry, PharmaceuticalDelayed-Action PreparationsDidanosineModels, StatisticalTabletsJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Carla Sánchez-Lafuente, Sandra Furlanetto, Mercedes Fernández-Arévalo, Josefa Alvarez-Fuentes, Antonio M Rabasco, M Teresa Faucci, Sergio Pinzauti, Paola Mura. 2002-04-26. Didanosine extended-release matrix tablets: optimization of formulation variables using statistical experimental design.. https://doi.org/10.1016/s0378-5173(02)00028-5

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2021

Drug resistance mutations in HIV provirus are associated with defective proviral genomes with hypermutation.

BACKGROUND: HIV proviral sequencing overcomes the limit of plasma viral load requirement by detecting all the 'archived mutations', but the clinical relevance remains to be evaluated. METHODS: We included 25 participants with available proviral sequences (both intact and defective sequences available) and utilized the genotypic sensitivity score (GSS) to evaluate the level of resistance in their provirus and plasma virus. Defective sequences were further categorized as sequences with and without hypermutations. Personalized GSS score and total GSS score were calculated to evaluate the level of resistance to a whole panel of antiretroviral therapies and to certain antiretroviral therapy that a participant was using. The rate of sequences with drug resistance mutations (DRMs) within each sequence compartment (intact, defective and plasma viral sequences) was calculated for each participant. RESULTS: Defective proviral sequences harbored more DRMs than other sequence compartments, with a median DRM rate of 0.25 compared with intact sequences (0.0, P&#x200a;=&#x200a;0.014) and plasma sequences (0.095, P&#x200a;=&#x200a;0.30). Defective sequences with hypermutations were the major source of DRMs, with a median DRM rate of 1.0 compared with defective sequences without hypermutations (0.042, P&#x200a;<&#x200a;0.001). Certain Apolipoprotein B Editing Complex 3-related DRMs including reverse transcriptase gene mutations M184I, E138K, M230I, G190E and protease gene mutations M46I, D30N were enriched in hypermutated sequences but not in intact sequences or plasma sequences. All the hypermutated sequences had premature stop codons due to Apolipoprotein B Editing Complex 3. CONCLUSION: Proviral sequencing may overestimate DRMs as a result of hypermutations. Removing hypermutated sequences is essential in the interpretation of proviral drug resistance testing.

Anti-HIV Agents↗
PubMed2007

Early initiation of antiretroviral therapy: the current best way to reduce liver-related deaths in HIV/hepatitis C virus-coinfected patients.

Approximately 25% to 35% of HIV-infected persons in developed countries are coinfected with hepatitis C virus (HCV). HCV liver disease is accelerated by HIV coinfection, especially at low CD4 cell counts. Highly active antiretroviral therapy (HAART) dramatically reduces HIV-related mortality, and liver disease has emerged as a major cause of death in HIV/HCV-coinfected persons. Anti-HCV therapy with pegylated interferon plus ribavirin can cure HCV infection in up to 40% of coinfected patients; however, only approximately 10% of coinfected patients are considered candidates. Hence, HCV therapy cures approximately 4% of coinfected patients. Eleven cohort studies have shown that HAART is associated with a reduced rate of progression of HCV liver disease, and 4 of these studies have demonstrated a reduction in liver-related mortality. Although offering HCV therapy to the few eligible HIV/HCV-coinfected patients is important, early initiation of HAART in coinfected patients has a greater public health impact in reducing liver-related mortality than in curing HCV infection in approximately 4% of these patients.

Anti-HIV Agents↗
PubMed2007

Genotypic resistance of archived and circulating viral strains in the blood of treated HIV-infected individuals.

The aim of this study was to evaluate patterns of antiretroviral resistance of HIV-1 in peripheral blood mononuclear cells (PBMCs) and in the plasma of patients whose therapeutic regimen is failing. Plasma and PBMC samples were collected from 95 HIV-infected patients undergoing long-term treatment. Genotyping of the reverse transcriptase (RT) and protease genes of HIV-1 was undertaken using the fluorescent dideoxy-terminator method. Comparison of the amino acid sequence of the RT and protease genes in cell-associated variants of HIV-1 with that of the plasma revealed that 62 of the 95 patients' samples tested exhibited different genotypic resistance patterns (discordant samples [DSs]). In 27% of samples, the patterns of resistance detected were concordant in both compartments. In 51% of DSs, the greatest number of mutations was found in plasma; however, in 37% of DSs, greater numbers of mutations were found in PBMC DNA. The HIV mutation patterns detected in plasma do not necessarily reflect those found in the cell-associated compartment. The observation that the cellular compartment may contain an archive of the resistance variant makes this reservoir an interesting substrate for analysis of the "resistance potential" in a given patient.

Anti-HIV Agents↗