Journal article
Gastroretentive Delivery Approach to Address pH-Dependent Degradation of (+)- and (-)-Phenserine
AAPS PharmSciTech, Vol.25(7), 198
08/27/2024
DOI: 10.1208/s12249-024-02903-w
PMID: 39192157
Abstract
(-)-Phenserine (“phenserine”) and (+)-phenserine (posiphen; buntanetap) are longer-acting enantiomeric analogs of physostigmine with demonstrated promise in the treatment of Alzheimer’s and Parkinson’s diseases. Both enantiomers have short plasma half-lives, and their pharmacokinetics might be improved through the use of either once or twice-daily administration of an extended-release dosage form. Phenserine was observed to form a colored degradation product in near-neutral and alkaline pH environments, and at pH 7, the half-life of posiphen was determined to be ~ 9 h (40 °C). To limit luminal degradation which would reduce bioavailability, a gastroretentive tablet composed of a polyethylene oxide-xanthan gum matrix was developed. When placed in simulated gastric fluid (pH 1.2), approximately 70% of the phenserine was released over a 12 h period, and no degradants were detected in the release medium. In comparison, a traditional hydrophilic-matrix, extended-release tablet showed measurable amounts of phenserine degradation in a pH 7.2 medium over an 8 h release interval. These results confirm that a gastroretentive tablet can reduce the luminal degradation of phenserine or posiphen by limiting exposure to neutral pH conditions while providing sustained release of the drug over at least 12 h. Additional advantages of the gastroretentive tablet include reduced gastric and intestinal concentrations of the drug resulting from the slower release from the gastroretentive tablet which may also limit the occurrence of the dose-limiting GI side effects previously observed with immediate-release phenserine capsules.
Graphical Abstract
Details
- Title: Subtitle
- Gastroretentive Delivery Approach to Address pH-Dependent Degradation of (+)- and (-)-Phenserine
- Creators
- Pratishtha Verma - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of IowaLeyla Rezaei - University of IowaRamprakash Govindarajan - University of IowaNigel H. Greig - National Institute on AgingMaureen D. Donovan - Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa
- Resource Type
- Journal article
- Publication Details
- AAPS PharmSciTech, Vol.25(7), 198
- Publisher
- Springer International Publishing
- DOI
- 10.1208/s12249-024-02903-w
- PMID
- 39192157
- ISSN
- 1530-9932
- eISSN
- 1530-9932
- Grant note
- NIH: 75N95D20P00146
This work was supported in part by funding from NIH 75N95D20P00146.
- Language
- English
- Date published
- 08/27/2024
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984699520802771
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