Related Experiment Video
Updated: Aug 12, 2026
14:37
High-throughput Synthesis of Carbohydrates and Functionalization of Polyanhydride Nanoparticles
Published on: July 6, 2012
Bottom-up particle engineering via solvent-mediated polymorphic transformation: a novel strategy for pharmaceutical
Elizabeth Horstman1, Ernest Carra1, Vijay Dhand2
1Gilead Sciences, Foster City, CA 94404, USA.
International Journal of Pharmaceutics
|August 10, 2026
Summary
Researchers engineered bictegravir particles using a novel bottom-up strategy. This approach overcame poor flowability, enabling practical manufacturing for long-acting injectable formulations.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
- Chemical Engineering
Background:
- Bictegravir free acid possesses a complex polymorph landscape, posing manufacturing challenges.
- Initial top-down particle engineering (crystallization/micronization) resulted in poor API flowability for long-acting injectable (LAI) formulation development.
Purpose of the Study:
- To develop a novel bottom-up particle engineering strategy for bictegravir API.
- To overcome processability challenges associated with bictegravir's complex polymorph landscape.
- To achieve critical quality attributes for LAI formulation manufacturing.
Main Methods:
- Utilized solvent-mediated polymorphic transformation (SMPT) using hydrated forms as precursors.
- Developed two SMPT processes to convert metastable forms to the most stable polymorph.
- Employed Raman spectroscopy for real-time transformation monitoring.
- Applied multivariate analysis to optimize particle size and operating conditions.
Main Results:
- Achieved API with small particle size and narrow, unimodal particle size distribution.
- Significantly enhanced API flowability, meeting LAI formulation requirements.
- Successfully converted metastable polymorphs and pseudopolymorphs to the stable form.
Conclusions:
- A novel bottom-up particle engineering strategy effectively addresses bictegravir's complex polymorph landscape.
- Harnessing hydrated forms and SMPT provides a versatile method for improving API processability.
- This methodology is applicable to compounds with accessible hydrates and a metastable-to-stable SMPT pathway yielding favorable crystal habits.
Related Concept Videos
01:16Bioavailability Enhancement: Drug Solubility Enhancement
Bioavailability is a critical factor in determining a drug's effectiveness. It refers to the proportion of a drug that enters the circulation when introduced into the body and is, as a result, able to have an active effect. Enhancing bioavailability is essential for drugs with poor solubility, as it can significantly impact their therapeutic efficacy. Various methods are employed to increase the solubility of drugs, thereby enhancing their bioavailability.Micronization and nanonization are...
01:27Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence
Changes in polymorphic forms can significantly influence the bioavailability of poorly soluble drugs. Although the FDA defines pharmaceutical equivalence based on having the same active ingredient, dosage form, and route of administration, it does not automatically disqualify products with different polymorphic forms. This means two products with different polymorphs can still be deemed pharmaceutically equivalent. However, polymorphic differences can affect properties like wettability,...
01:24Site-Targeted Drug Delivery Systems: Polymeric Carriers
Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...