Powder for reconstitution of the anti-HIV-1 drug TMC278 - Formulation development, stability and animal studies
| Autor: | Murali Pendela, Pieter Van Remoortere, Wigerinck Piet Tom Bert Paul, Hilde De Man, Laurent Schueller, Marie-Paule Bouche, Elke Van Gyseghem, Jan Rosier, Guy Van den Mooter, Gerben Albert Eleutherius Van 'T Klooster, Lieven Baert, Jos Hoogmartens, Erwin Adams |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Anti-HIV Agents Chemistry Pharmaceutical Pharmaceutical Science Administration Oral Biological Availability Pharmacology Excipients chemistry.chemical_compound Dogs Pharmacokinetics Drug Stability In vivo Nitriles medicine Animals Technology Pharmaceutical Solubility Supersaturation Drug Carriers Chromatography Reverse-transcriptase inhibitor business.industry Rilpivirine General Medicine HIV Reverse Transcriptase Bioavailability Pyrimidines chemistry Reverse Transcriptase Inhibitors Powders Drug carrier business Biotechnology medicine.drug Tablets |
| Zdroj: | European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 70(3) |
| ISSN: | 0939-6411 |
| Popis: | Powders for reconstitution of the next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278 with low water solubility were developed by using a spray-dry technology. Their flexible dosing ability makes them suitable for patients looking for a different approach for antiretroviral (ARV) therapy. The selection of formulation excipients was based on their potential to create and maintain supersaturation solubility of TMC278 in 0.01 M HCl. Suitable water-soluble carriers for TMC278 were selected by a supersaturation screening to formulate powders for reconstitution by spray-drying. The selected powders for reconstitution were compared to clinical tablets of TMC278.HCl, in vitro using dissolution and stability testing, and in vivo through administration to beagle dogs, fed immediately after dosing. The spray-dried powders for reconstitution made up of TMC278/PVP-VA 64 1:9 (w/w) and TMC278/PVP-VA 64/Cremophor EL 1:8.5:0.5 (w/w/w) showed ease of suspendability, nearly complete dissolution of the drug and acceptable stability after one month storage at 25 and 40 degrees C. In dogs, TMC278 was more slowly absorbed from tablets than from the suspended powders for reconstitution. Compared to the tablet, the relative bioavailability obtained with the powders ranged between 69% and 89% for TMC278/PVP-VA 64 1:9 (w/w) and between 85% and 157% for TMC278/PVP-VA 64/Cremophor EL 1:8.5:0.5 (w/w/w). The absence of differences in vivo and in vitro between the powders made an eventual choice very difficult, yet their advantageous in vivo behaviour and flexible dosing possibility may provide a starting point for paediatric formulations. |
| Databáze: | OpenAIRE |
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