Journal article
Balancing Solid-State Stability and Dissolution Performance of Lumefantrine Amorphous Solid Dispersions: The Role of Polymer Choice and Drug–Polymer Interactions
Molecular pharmaceutics, Vol.19(2), pp.392-413
02/07/2022
DOI: 10.1021/acs.molpharmaceut.1c00481
PMID: 34494842
Abstract
Amorphous solid dispersions (ASDs) are of great interest due to their ability to enhance the delivery of poorly soluble drugs. Recent studies have shown that, in addition to acting as a crystallization inhibitor, the polymer in an ASD plays a role in controlling the rate of drug release, notably in congruently releasing formulations, where both the drug and polymer have similar normalized release rates. The aim of this study was to compare the solid-state stability and release performance of ASDs when formulated with neutral and enteric polymers. One neutral (polyvinylpyrrolidone–vinyl acetate copolymer, PVPVA) and four enteric polymers (hypromellose acetate succinate; hypromellose phthalate; cellulose acetate phthalate, CAP; methacrylic acid–methyl methacrylate copolymer, Eudragit L 100) were used to formulate binary ASDs with lumefantrine, a hydrophobic and weakly basic antimalarial drug. The normalized drug and polymer release rates of lumefantrine–PVPVA ASDs up to 35% drug loading (DL) were similar and rapid. No drug release from PVPVA systems was detected when the DL was increased to 40%. In contrast, ASDs formulated with enteric polymers showed a DL-dependent decrease in the release rates of both the drug and polymer, whereby release was slower than for PVPVA ASDs for DLs < 40% DL. Drug release from CAP and Eudragit L 100 systems was the slowest and drug amorphous solubility was not achieved even at 5% DL. Although lumefantrine–PVPVA ASDs showed fast release, they also showed rapid drug crystallization under accelerated stability conditions, while the ASDs with enteric polymers showed much greater resistance to crystallization. This study highlights the importance of polymer selection in the formulation of ASDs, where a balance between physical stability and dissolution release must be achieved.
Details
- Title: Subtitle
- Balancing Solid-State Stability and Dissolution Performance of Lumefantrine Amorphous Solid Dispersions: The Role of Polymer Choice and Drug–Polymer Interactions
- Creators
- Tze Ning Hiew - Purdue University West LafayetteDmitry Y Zemlyanov - Purdue University West LafayetteLynne S Taylor - Purdue University West Lafayette
- Resource Type
- Journal article
- Publication Details
- Molecular pharmaceutics, Vol.19(2), pp.392-413
- DOI
- 10.1021/acs.molpharmaceut.1c00481
- PMID
- 34494842
- NLM abbreviation
- Mol Pharm
- ISSN
- 1543-8384
- eISSN
- 1543-8392
- Publisher
- American Chemical Society
- Grant note
- DOI: 10.13039/100000865, name: Bill and Melinda Gates Foundation, award: OPP1159809; DOI: 10.13039/100006241, name: IPEC-Americas Foundation
- Language
- English
- Date published
- 02/07/2022
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984365882102771
Metrics
28 Record Views