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Multiple tamping effects on drug dissolution from capsules filled on a dosing-disk type automatic capsule filling
K B Shah1, L L Augsburger, K Marshall
1Department of Pharmaceutics, School of Pharmacy, University of Maryland, Baltimore 21201, USA.
Journal of Pharmaceutical Sciences
|August 1, 1987
Summary
Capsule filling parameters like tamping force and number of tamps significantly impact drug dissolution rates. Formulation excipients, such as disintegrants, can mitigate these effects, optimizing drug release for poorly soluble drugs.
Area of Science:
- Pharmaceutical Technology
- Drug Delivery Systems
- Physical Pharmacy
Background:
- Capsule filling processes involve critical parameters influencing drug product performance.
- Understanding the impact of tamping on drug dissolution is crucial for consistent pharmaceutical manufacturing.
- Hydrochlorothiazide, a low-dose, poorly soluble drug, serves as a relevant model for dissolution studies.
Purpose of the Study:
- To investigate the influence of tamping force and number of tamps on hydrochlorothiazide dissolution from capsules.
- To evaluate the role of different fillers (dicalcium phosphate dihydrate, anhydrous lactose) and a disintegrant (croscarmellose sodium) in modulating these effects.
- To elucidate the dissolution mechanism of hydrochlorothiazide from specific capsule formulations.
Main Methods:
- Utilized an instrumented dosing-disk automatic capsule filling machine (Hofliger-Karg).
- Studied hydrochlorothiazide dissolution under varying numbers of tamps and tamping forces.
- Employed dicalcium phosphate dihydrate and anhydrous lactose as fillers, with and without croscarmellose sodium.
- Analyzed powder consolidation using mercury intrusion pore size distribution.
Main Results:
- Increased tamping generally slowed dissolution, particularly with dicalcium phosphate dihydrate.
- Higher compression forces improved release with anhydrous lactose but hindered it with dicalcium phosphate dihydrate.
- Croscarmellose sodium diminished the impact of tamping parameters and enhanced dissolution, especially for dicalcium phosphate formulations.
- Hydrochlorothiazide dissolution from dicalcium phosphate formulations without disintegrant followed a diffusion-from-insoluble-matrix model.
Conclusions:
- Capsule filling parameters and formulation composition significantly affect drug dissolution.
- Disintegrants play a vital role in overcoming processing-induced changes and enhancing drug release.
- Powder consolidation appears to plateau after two tamps at forces of 100 or 200 N.