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Influence of Low-Molecular-Weight Excipients on the Phase Behavior of PVPVA64 Amorphous Solid Dispersions

Influence of Low-Molecular-Weight Excipients on the Phase Behavior of PVPVA64 Amorphous Solid Dispersions

Kristin Lehmkemper, Samuel O Kyeremateng, Matthias Degenhardt, Gabriele Sadowski

Pharm Res. 2018 Jan 5;35(1):25.

PMID: 29305717

Abstract:

Purpose:
The oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs) can be improved by the preparation of amorphous solid dispersions (ASDs) where the API is dissolved in polymeric excipients. Desired properties of such ASDs like storage stability, dissolution behavior, and processability can be optimized by additional excipients. In this work, the influence of so-called low-molecular-weight excipients (LMWEs) on the phase behavior of ASDs was investigated.
Method:
Binary ASDs of an amorphous API, naproxen (NAP) or acetaminophen (APAP), embedded in poly-(vinylpyrrolidone-co-vinyl acetate) (PVPVA64) were chosen as reference systems. Polyethylene glycol 1500 (PEG1500), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS1000), propylene glycol monocaprylate type II (Capryol™ 90), and propylene glycol monolaurate type I (Lauroglycol™ FCC) were used as LMWEs. The API solubility in the excipients and the glass-transition temperature of the ASDs were modeled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) and the Kwei equation, respectively, and compared to corresponding experimental data.
Results:
The API solubility curves in ternary systems with 90/10 wt%/wt% PVPVA64/LMWE ratios were very close to those in pure PVPVA64. However, the glass-transition temperatures of API/PVPVA64/LMWE ASDs were much lower than those of API/PVPVA64 ASDs. These effects were determined experimentally and agreed with the predictions using the PC-SAFT and Kwei models.
Conclusion:
The impact of the LMWEs on the thermodynamic stability of the ASDs is quite small while the kinetic stability is significantly decreased even by small LMWE amounts. PC-SAFT and the Kwei equation are suitable tools for predicting the influence of LMWEs on the ASD phase behavior.

Chemicals Related in the Paper:

Catalog Number	Product Name	CAS Number	Price
AP25322683-B	Polyethylene glycol 1500	25322-68-3	Price
AP37321623	Propylene glycol monolaurate type II	37321-62-3	Price
CS31042957	Propylene glycol monocaprylate type I		Price
CS31042958	Propylene glycol monocaprylate type II		Price
CS31042962	Propylene glycol monolaurate type I		Price

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