ABSTRACT
The present investigation was aimed to develop self-nanoemulsifying tablets (SNETs) as novel nanosized solid oral dosage forms for Irbesartan (IRB). In the first part of the investigation, IRB-loaded self-nanoemulsifying drug delivery systems (SNEDDS) were developed using Capryol 90 - Cremophor RH40 - Transcutol P as three component (oil - surfactant - cosurfactant) SNEDDS system. On the basis of ternary phase diagram IRB-loaded SNEDDS were optimized by using Design of Experiments (DoE) and Principal component analysis (PCA) with amount of oil and surfactant: cosurfactant ratio (Km) as factors. The optimized batch of IRB-loaded SNEDDS comprised of 31.62% w/w of Capryol 90 as oil phase, 49.90% w/w Cremophor RH40 as surfactant and 18.48% w/w of Transcutol P as cosurfactant exemplified a mean globule size as 23.94 nm. Further, with an aim to provide enhanced patient compliance the optimized batch of liquid SNEDDS was transformed into SNETs by liquisolid compaction technique. Solid state characterization of IRB-loaded liquisolid mixtures revealed a decrease in the magnitude of crystallinity of IRB. The results of in vitro drug release study of optimized batch of IRB-loaded SNET illustrated a remarkable improvement in the dissolution rate as compared to marketed tablets (Avapro® 75). The results of in vivo pharmacokinetic study on Wister rats revealed 1.78-fold enhancement in oral bioavailability for IRB-loaded SNETs against marketed tablets. The present study proposed SNEDDS as one of the suitable approach for developing nanosized solid oral dosage forms of poorly water soluble drugs like Irbesartan.
Subject(s)
Biphenyl Compounds/chemistry , Biphenyl Compounds/metabolism , Emulsions/chemistry , Emulsions/metabolism , Nanoparticles/chemistry , Tablets/chemistry , Tablets/metabolism , Tetrazoles/chemistry , Tetrazoles/metabolism , Administration, Oral , Animals , Biological Availability , Drug Carriers/chemistry , Drug Delivery Systems/methods , Irbesartan , Male , Nanoparticles/metabolism , Oils/chemistry , Particle Size , Rats , Rats, Wistar , Solubility , Surface-Active Agents/chemistryABSTRACT
Poor mechanical properties of crystalline drug particles require wet granulation technique for tablet production which is uneconomical, laborious, and tedious. The present investigation was aimed to improve flow and mechanical properties of racecadotril (RCD), a poorly water soluble antidiarrheal agent, by a crystallo-co-agglomeration (CCA) technique. The influence of various excipients and processing conditions on formation of directly compressible agglomerates of RCD was evaluated. Principal component analysis and Box-Behnken experimental design was implemented to optimize the agglomerates with good micromeritics and mechanical properties. The overall yield of the process was 88-98% with size of agglomerates between 351 and 1214 µm. Further, higher rotational speed reduced the size of agglomerates and disturbed sphericity. The optimized batch of agglomerates exhibited excellent flowability and crushing strength. The optimized batch of RCD agglomerates was characterized by fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry and gas chromatography which illustrated absence of drug-excipient interaction with minimal entrapment of residual solvent. Hence, it may be concluded that both excipients and processing conditions played a vital role to prepare spherical crystal agglomerates of RCD by CCA and it can be adopted as an excellent alternative to wet granulation.
