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In vitro-in vivo evaluation of supercritical processed solid dispersions: permeability and viability assessment in Caco-2 cells.
J Pharm Sci. 2004 Dec; 93(12):2985-93.JP

Abstract

In this study improvement in the bioavailability of carbamazepine (CBZ) prepared as solid dispersions by conventional solvent evaporation and supercritical fluid (SCF) processing methods was assessed, along with the elucidation of the mechanism of improved absorption. Solid dispersions of CBZ in polyethylene glycol (PEG) with either Gelucire 44/14 or vitamin E-TPGS (TPGS) were evaluated by intrinsic dissolution. Directional transport through Caco-2 cell monolayers was determined in the presence and absence of TPGS. Cell viability in presence of various concentrations of amphiphilic carriers was seen. In vivo oral bioavailability was determined in rats. The apparent intrinsic dissolution rates (IDR) of both conventional- and SCF-CBZ/PEG 8000/TPGS solid dispersions were increased by 13- and 10.6-fold, respectively, relative to neat CBZ. CBZ was not a substrate of P-glycoprotein. Higher CBZ permeability was seen in presence of 0.1% TPGS. Cell viability studies showed significant cytotoxicity only at or above 0.1% amphiphilic carrier. Supercritical treated formulation (without amphiphilic carrier) displayed oral bioavailability on par with those conventional solid dispersions augmented with amphiphilic carriers. An in vitro-in vivo correlation was seen between IDR and the AUC of the various CBZ solid dispersions. Bioavailability of CBZ was more a function of dissolution as opposed to membrane effects. Although bioavailability from SCF processed dispersions was better than conventionally processed counterparts (except for one formulation containing Gelucire 44/14), an interaction of processing method and inclusion of an amphiphilic carrier, rather by one factor alone contributed to optimal absorption, thus giving contradictory results for Gelucire 44/14 and TPGS formulations.

Authors+Show Affiliations

College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Parkway, Jamaica, New York 11439, USA. squillae@stjohns.eduNo affiliation info available

Pub Type(s)

Comparative Study
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15468328

Citation

Sethia, Sundeep, and Emilio Squillante. "In Vitro-in Vivo Evaluation of Supercritical Processed Solid Dispersions: Permeability and Viability Assessment in Caco-2 Cells." Journal of Pharmaceutical Sciences, vol. 93, no. 12, 2004, pp. 2985-93.
Sethia S, Squillante E. In vitro-in vivo evaluation of supercritical processed solid dispersions: permeability and viability assessment in Caco-2 cells. J Pharm Sci. 2004;93(12):2985-93.
Sethia, S., & Squillante, E. (2004). In vitro-in vivo evaluation of supercritical processed solid dispersions: permeability and viability assessment in Caco-2 cells. Journal of Pharmaceutical Sciences, 93(12), 2985-93.
Sethia S, Squillante E. In Vitro-in Vivo Evaluation of Supercritical Processed Solid Dispersions: Permeability and Viability Assessment in Caco-2 Cells. J Pharm Sci. 2004;93(12):2985-93. PubMed PMID: 15468328.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro-in vivo evaluation of supercritical processed solid dispersions: permeability and viability assessment in Caco-2 cells. AU - Sethia,Sundeep, AU - Squillante,Emilio, PY - 2004/10/7/pubmed PY - 2005/4/13/medline PY - 2004/10/7/entrez SP - 2985 EP - 93 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 93 IS - 12 N2 - In this study improvement in the bioavailability of carbamazepine (CBZ) prepared as solid dispersions by conventional solvent evaporation and supercritical fluid (SCF) processing methods was assessed, along with the elucidation of the mechanism of improved absorption. Solid dispersions of CBZ in polyethylene glycol (PEG) with either Gelucire 44/14 or vitamin E-TPGS (TPGS) were evaluated by intrinsic dissolution. Directional transport through Caco-2 cell monolayers was determined in the presence and absence of TPGS. Cell viability in presence of various concentrations of amphiphilic carriers was seen. In vivo oral bioavailability was determined in rats. The apparent intrinsic dissolution rates (IDR) of both conventional- and SCF-CBZ/PEG 8000/TPGS solid dispersions were increased by 13- and 10.6-fold, respectively, relative to neat CBZ. CBZ was not a substrate of P-glycoprotein. Higher CBZ permeability was seen in presence of 0.1% TPGS. Cell viability studies showed significant cytotoxicity only at or above 0.1% amphiphilic carrier. Supercritical treated formulation (without amphiphilic carrier) displayed oral bioavailability on par with those conventional solid dispersions augmented with amphiphilic carriers. An in vitro-in vivo correlation was seen between IDR and the AUC of the various CBZ solid dispersions. Bioavailability of CBZ was more a function of dissolution as opposed to membrane effects. Although bioavailability from SCF processed dispersions was better than conventionally processed counterparts (except for one formulation containing Gelucire 44/14), an interaction of processing method and inclusion of an amphiphilic carrier, rather by one factor alone contributed to optimal absorption, thus giving contradictory results for Gelucire 44/14 and TPGS formulations. SN - 0022-3549 UR - https://www.unboundmedicine.com/medline/citation/15468328/In_vitro_in_vivo_evaluation_of_supercritical_processed_solid_dispersions:_permeability_and_viability_assessment_in_Caco_2_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(16)39316-9 DB - PRIME DP - Unbound Medicine ER -