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Increasing Drug Loading of Weakly Acidic Telmisartan in Amorphous Solid Dispersions through pH Modification during
Stephen A Thompson1, Daniel A Davis1, Chaeho Moon1
1Division of Molecular Pharmaceutics and Drug Delivery, The University of Texas at Austin College of Pharmacy, Austin, Texas 78712, United States.
Molecular Pharmaceutics
|November 30, 2021
Summary
Maximizing drug loading in amorphous solid dispersions (ASDs) reduces pill burden. Incorporating bases during hot-melt extrusion (HME) significantly increased telmisartan loading in ASDs without impacting dissolution.
Area of Science:
- Pharmaceutical Technology
- Drug Delivery Systems
- Materials Science
Background:
- High pill burden from oral medications impacts patient adherence and health outcomes.
- Maximizing active pharmaceutical ingredient (API) loading in oral dosage forms is crucial for reducing pill burden.
- Poorly water-soluble APIs present challenges for high drug loading in amorphous solid dispersions (ASDs) without compromising performance.
Purpose of the Study:
- To develop a strategy for maximizing the drug loading of pH-dependent APIs in ASDs via hot-melt extrusion (HME).
- To investigate the effect of incorporating bases on telmisartan drug loading and dissolution performance in ASDs.
- To assess the stability of the polymer (Soluplus) when extruded with bases.
Main Methods:
- Amorphous solid dispersions (ASDs) of telmisartan and Soluplus were prepared using hot-melt extrusion (HME) with varying concentrations of bases.
- Drug loading and physical form (amorphous vs. crystalline) were analyzed.
- Dissolution testing was performed in biorelevant media.
- Solid-state nuclear magnetic resonance (ssNMR) was used to evaluate polymer stability.
Main Results:
- Without added bases, maximum telmisartan loading in ASDs was limited to 5% before crystallization.
- Incorporating strong bases (NaOH or KOH) enabled amorphous telmisartan loading up to 50% via HME.
- Dissolution testing showed maintained supersaturation for at least 20 hours with a 50% telmisartan ASD.
- ssNMR indicated NaOH caused Soluplus degradation via hydrolysis, while KOH did not.
Conclusions:
- Incorporating bases effectively increases the drug loading of pH-dependent APIs like telmisartan in ASDs produced by HME.
- This strategy enhances drug loading without compromising dissolution performance, offering a solution to reduce pill burden.
- Careful selection of bases is necessary, as some, like NaOH, can lead to polymer degradation.
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