Bioequivalence studies and sugar-based excipients effects on the properties of new generic ketoconazole tablets formulations and stability evaluation by using direct compression method.
In this work we described the development of a new solid oral formulation of ketoconazole, a broad-spectrum antifungal agent that belongs to the class II of Biopharmaceutics Classification System (BCS). The ketoconazole raw material supplier was selected to present a best flow and compactation. In addition we used direct compression and superdisintegrants associated to polyols to enhance the dissolution of the ketoconazole tablets. The dissolution was evaluated based in level C in vivo/in vitro correlation established. The best formulation was obtained with croscarmellose/maltose association that in the accelerated stability assays presented no differences on quality specifications and no drug-excipients interaction by DSC analyses. In this work it was possible to confirm the use of sugar-based excipients as suitable dissolution enhancers in pharmaceutical technology and real processes conditions.
Viçosa
Alessandra L
AL
TIF, Departamento de Medicamentos, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Chatah
Eliane N
EN
Santos
Tereza C
TC
Jones
Luiz F
LF
Dantas
Cide B
CB
Dornelas
Camila B
CB
Rodrigues
Carlos R
CR
Castro
Helena C
HC
Sousa
Valéria P
VP
Dias
Luiza R S
LR
Cabral
Lúcio M
LM
D000935:Antifungal Agents / Q000493:pharmacokinetics*; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D006244:Hardness; D006801:Humans; D007654:Ketoconazole / Q000493:pharmacokinetics*; D008320:Maltose / Q000737:chemistry; D012995:Solubility; D013607:Tablets / Q000032:analysis; D013810:Therapeutic Equivalency
D000935:Antifungal Agents; D005079:Excipients; D013607:Tablets; D008320:Maltose; D002266:Carboxymethylcellulose Sodium; D007654:Ketoconazole