Design and development of solid nanoparticulate dosage forms of telmisartan for bioavailability enhancement by integration of experimental design and principal component analysis

• Utilization of nanosuspension as a vehicle for oral delivery of telmisartan.
• Reduction in size of drug molecules and increase in effective surface area.
• Efficacious conversion of optimized formulations into tablets.
• Productive amalgamation of NDDS with the conventional dosage form.

Aim of the present investigation was to develop nanoparticulate solid oral dosage forms of a poorly water soluble antihypertensive agent, telmisartan (TLM) by converting the optimized batch of drug loaded nanosuspensions into a tablet dosage form using lyophilization technique. The TLM loaded nanosuspensions were optimized by implementation of 32 full factorial design along with principal component analysis (PCA) with concentration of stabilizer and amount of milling agents as factors. The optimized batch of TLM loaded nanosuspension exhibited a mean particle size of 334.67 ± 10.43 nm. The results of various instrumental techniques illustrated retention of drug crystallinity after milling and lyophilization. The results of in vitro drug release study of tablets containing drug nanocrystals revealed remarkable improvement in the dissolution rate as compared to the marketed tablet (Sartel® 20). The results of in vivo pharmacokinetic study on Wister rats revealed 1.5-fold enhancement in oral bioavailability for tablets containing TLM nanocrystals against the marketed tablets. The present study proposed nanosuspension as a suitable approach for developing nanosized solid oral dosage forms of poorly water soluble drugs like telmisartan using design of experiment and principal component analysis as two important paradigms of quality by design technique.

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