Pairwise Polymer Blends for Oral Drug Delivery

Abstract

Blends of polymers with complementary properties hold promise for addressing the diverse, demanding polymer performance requirements in amorphous solid dispersions (ASDs), but we lack comprehensive property understanding for blends of important ASD polymers. Herein, we prepare pairwise blends of commercially available polymers polyvinylpyrrolidone (PVP), the cationic acrylate copolymer Eudragit 100 (E100), hydroxypropyl methylcellulose acetate succinate (HPMCAS), carboxymethyl cellulose acetate butyrate (CMCAB), hydroxypropyl methylcellulose (HPMC), and the new derivative cellulose acetate adipate propionate (CAAdP). This study identifies miscible binary blends that may find use, for example, in ASDs for solubility and bioavailability enhancement of poorly water-soluble drugs. Differential scanning calorimetry, FTIR spectroscopy, and film clarity were used to determine blend miscibility. Several polymer combinations including HPMCAS/PVP, HPMC/CMCAB, and PVP/HPMC appear to be miscible in all proportions. In contrast, blends of E100/PVP and E100/HPMC showed a miscibility gap. Combinations of water-soluble and hydrophobic polymers like these may permit effective balancing of ASD performance criteria such as release rate and polymer-drug interaction to prevent nucleation and crystal growth of poorly soluble drugs. Miscible polymer combinations described herein will enable further study of their drug delivery capabilities, and provide a potentially valuable set of ASD formulation tools.

Effect of Temperature and Moisture on the Physical Stability of Binary and Ternary Amorphous Solid Dispersions of Celecoxib

“…36 For the PVP:HPMCAS films, clear signs of miscibility between the 2 polymers could be observed based on evidence of hydrogen-bonding interactions, in agreement with previous reports. 37 The PVP carbonyl peak at 1682 cm À1 developed a shoulder at 1643 cm À1 , assigned to the C¼O of PVP hydrogen bonded to the carboxylic acid OH group of HPMCAS (Fig. 3).…”

Unravelling the Miscibility of Poly(2-oxazoline)s: A Novel Polymer Class for the Formulation of Amorphous Solid Dispersions

“…Since little was known about the miscibility behaviour of the different PAOx, besides our recent report on phase separation of PEtOx-PPrOx blends [ 23 ], formulations containing only PAOx were prepared through spray drying or film casting in order to assess the miscibility of both PAOx combinations in the absence of API. Various authors have already highlighted the importance of understanding the miscibility and phase behaviour of a binary carrier mixture in order to fully and correctly understand that of the ternary dispersions with API [ 31 , 32 , 33 ]. Next to that, addition of the API, a third component, could affect the miscibility behaviour of the two polymers.…”

Insoluble Polymers in Solid Dispersions for Improving Bioavailability of Poorly Water-Soluble Drugs

“…Ternary SDs are effective strategies for further enhancing the dissolution of poorly water-soluble drugs [ 68 , 82 , 83 , 84 , 85 ]. Enteric coating polymers have been investigated by this approach [ 86 , 87 ]. Ohyagi et al combined hypromellose and Eudragit ® L 100 (or a methacrylic acid copolymer) and showed that the resulting ternary SDs had improved dissolution compared to those of single-polymer SDs [ 86 ].…”