Stability Enhancement of Drug Layered Pellets in a Fixed Dose Combination Tablet

Abstract

Abstract. The purpose of this research was to develop a stable fixed dose combination tablet for a model DPP-IV inhibitor and metformin hydrochloride. The dipeptidyl peptidase IV (DPP-IV) inhibitor was particularly challenging to formulate due to its significant chemical instability and moisture sensitivity. Various formulation strategies were investigated and placed on accelerated stability to determine the lead approach and critical quality attributes. The lead formulation investigated was a drug layered pellet containing the DPP-IV inhibitor, which was further coated with various seal coats and moisture barriers, then compressed into a tablet with compression aids and granulated metformin hydrochloride. The investigations revealed that the drug layered pellets compressed into a fixed dose combination tablet yielded a unique stability enhancement. The stability was highly dependent on the final tablet water content and could be further improved by the addition of moisture barrier coatings. A fundamental understanding of the key critical quality attributes for the fixed dose combination product containing a DPP-IV inhibitor and metformin hydrochloride as an oral solid dosage form were established. This research identified a formulation approach to enable a successful commercial product to be developed.

<p>A Comprehensive Review on Pharmaceutical Film Coating: Past, Present, and Future</p>

“…Also, the use of such barriers could decrease potential negative interaction with another API in a fixed-dose combination tablet. 22 Evidently, FC procedures based on aqueous formulation can still show serious problems and threats toward moisture-sensitive APIs. These challenges and problems could be fixed involving organic solvents in the coating formulation.…”

Physical characterization of multiparticulate systems

“…Obtention of immediate-release systems, with a focus on masking drug flavor (Hamedelniel, Bajdik, Pintye-Hódi, 2010;Issa et al, 2012b;Patel, Patel, Patel, 2010);  Controlled-release (Abbaspour, Sadeghi, Garekani, 2008;Bialleck, Rein, 2011;Cantor, Hoag, Augsburger, 2009a;Cantor, Hoag, Augsburger, 2009b;Franc et al, 2015;Ghanam, Kleinebudde, 2011;Ghosh, Chakraborty, 2013;Han et al, 2013;Heckötter et al, 2011;Hung et al, 2015;Ríos, Ghaly, 2015;Roblegg et al, 2011;Szkutnik-Fiedler et al, 2014;Wang et al, 2015;Xu, Liew, Heng, 2015;You et al, 2014);  Improvement in dissolution of poorly soluble drugs (Abdalla, Mader, 2007;Abdalla, Klein, Mader, 2008;Chopra, Venkatesan, Betageri, 2013;Ibrahim, El-Badry, 2014;Lu et al, 2009;Patel et al, 2016);  Gastro-retentive systems/ floating systems (Amrutkar, Chaudhari, Patil, 2012;Li et al, 2014;Pagariya, Patil, 2013;Qi et al, 2015;Zhang et al, 2012);  Enteric release/gastro-resistant systems (Andreo-Filho et al, 2009;Ghanam, Kleinebudde, 2011;Pund et al, 2010);  Improvement of plant extract or active ingredient stability (Araújo-Junior et al, 2013;Beringhs et al, 2012;Bu...…”