Optimization of a Dissolution Method in Early Development Based on IVIVC Using Small Animals: Application to a BCS Class II Drug

Abstract

The aim of the present study was to develop optimal dissolution conditions for a BCS Class II drug in early development. The model drug efavirenz was formulated in two dosage forms: a classical immediate-release suspension and modified-release cubosomes. Dissolution studies were carried out in classical and biorelevant media adapted to early development using animal models to confirm the in vitro findings. The percentage drug dissolved was calculated in all media, and the percentage absorbed was calculated from in vivo data. Level A IVIVC was investigated in all media, and the best one selected based on the highest r 2 value. Optimal dissolution media that could be used as starting points for further development are 0.5% SLS in water for cubosomes and fasted-state simulated intestinal fluid (FaSSIF) for suspensions. The predicted plasma profiles show appropriate contour, and the internal prediction error was at most 12% for the predicted parameters C max and AUC. Thus, a simple approach was used for developing IVIVC based on animal in vivo data, which can be used as a quick and simple alternative tool in early development stage depending on which dissolution method can be optimized even before human studies.

Three Dimensional Printing by Hot-Melt Extrusion; New Era for Development of Personalized Medicines and Continuous Manufacturing of Pharmaceuticals

“…In 2015 first t drug manufactured by using 3D printing is approved by the FDA. 4 This is strong proof for development of new pharmaceutical products using 3D printing. It is also called as solid form of fabrication/ rapid prototyping/ additive manufacturing.…”

Selection and Parameters Affecting Dissolution Media

“…In such a scenario, it would be advantageous to have an in vitro dissolution test that could be utilized to predict in vivo behavior at different stages of formulation development. The rate-limiting step for the in vivo absorption of class 2 drugs is dissolution (38). Class 1 and 3 drugs display rapid or very rapid dissolution, and BCS provides for the waiver of in vivo bioavailability and bioequivalence testing for immediate-release solid dosage forms (39).…”

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“…The shake-flask method was used to carry out for the saturation solubility study. [30,31] The excess amount of plain active (SIM), melt-extruded, and spray-dried solid dispersion of SIM and Kollicoat ® Smartseal 30D was added into 10 ml separate violin an above solvent. These vials were shaken at 25 ± 2°C at 100 rpm for 48 h using an orbital shaker.…”