Titre du document / Document title

The impact of formulation and process changes on in vitro dissolution and the bioequivalence of piroxicam capsules

Auteur(s) / Author(s)

PISCITELLI D. A. ⁽¹⁾ ; BIGORA S. ⁽¹⁾ ; PROPST C. ⁽¹⁾ ; GOSKONDA S. ⁽¹⁾ ; SCHWARTZ P. ⁽²⁾ ; LESKO L. J. ⁽²⁾ ; AUGSBURGER L. ⁽¹⁾ ; YOUNG D. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Pharmaceutical Sciences, University of Maryland at Baltimore, 20 N. Pine St., Baltimore, Maryland, ETATS-UNIS
⁽²⁾ Food and Drug Administration, 1451 Rockville Pike, Rockville, Maryland, ETATS-UNIS

Résumé / Abstract

The purpose of this research was to determine the effect of major compositional changes on the bioavailability of piroxicam from immediate-release formulations filled in hard gelatin capsules. The capsules were manufactured according to a 2^5-1 + star point (resolution V) experimental design to investigate the effects of sodium lauryl sulfate level, magnesium stearate level, lactose/microcrystalline cellulose ratio, piroxicam particle size, and lubricant blending time. Sodium lauryl sulfate level, lactose level, and piroxicam particle size were the most important main effects affecting dissolution. Lubricant level and lubricant blending time were either not significant (5% level) or were among the lowest ranking offactors affecting dissolution in standardized pareto analysis. Three of these formulations exhibiting slow, medium, and fast dissolution were compared to a single lot of the Innovator (commercial) product in a small bioavailability study. The slow formulation did not meet the USP dissolution specification for piroxicam capsules. Compositionally, the experimental formulations represented major changes in piroxicam particle size, level of filler, and level of sodium lauryl sulfate. Sixteen healthy volunteers received each formulation (20 mg) in a four-way crossover design. The three Maryland manufactured formulations were bioequivalent with the commercial product and were also bioequivalent among themselves. The major changes incorporated into these formulations did not result in major differences in bioavailability. The dissolution profiles which discriminated between the formulations in vitro did not accurately represent the in vivo bioavailability results. The results of this study are part of the research database that supports SUPAC-IR, an FDA guidance that provides relaxed testing and filing requirements for scale-up and post-approval changes to immediate-releaase oral solid dosage forms.

Revue / Journal Title

Pharmaceutical development and technology   ISSN 1083-7450 

Source / Source

1998, vol. 3, n^o4, pp. 443-452 (20 ref.)

Langue / Language

Anglais

Editeur / Publisher

Informa Healthcare, New York, NY, ETATS-UNIS  (1996) (Revue)

Mots-clés anglais / English Keywords

Piroxicam ; Bioavailability ; Vehicle(excipient) ; Non steroidal antiinflammatory agent ; Hard capsule ; Pharmaceutical technology ; Dosage form ; Manufacturing process ; Immediate release form ; Chemical composition ; Comparative study ; In vitro ; Dissolution ; In vivo ; Human ; Pharmacokinetics ; Healthy subject ; Oxicam derivatives ; Bioequivalence ;

Mots-clés français / French Keywords

Piroxicam ; Biodisponibilité ; Excipient ; Antiinflammatoire non stéroïde ; Gélule ; Technologie pharmaceutique ; Forme pharmaceutique ; Procédé fabrication ; Forme libération immédiate ; Composition chimique ; Etude comparative ; In vitro ; Dissolution ; In vivo ; Homme ; Pharmacocinétique ; Individu sain ; Oxicam dérivé ; Bioéquivalence ;

Mots-clés espagnols / Spanish Keywords

Piroxicam ; Biodisponibilidad ; Excipiente(vehiculo) ; Antiinflamatorio no esteroide ; Cápsula dura ; Tecnología farmacéutica ; Forma farmacéutica ; Procedimiento fabricación ; Forma liberación inmediata ; Composición química ; Estudio comparativo ; In vitro ; Disolución ; In vivo ; Hombre ; Farmacocinética ; Individuo sano ; Oxicam derivado ; Bioequivalencia ;

Localisation / Location

INIST-CNRS, Cote INIST : 26544, 35400007292593.0030