The potential impact of concomitant alcohol consumption on in vivo release of drugs from modified release oral dosage forms is currently evincing much interest following the suspended marketing of Palladone (FDA Alert, July 2005). Human volunteer studies involving co-administration of drug and significant amounts of alcoholic beverages pose ethical and operational challenges. Consequently, in vitro studies, providing insight on release mechanisms in hydro-ethanolic media could guide formulation programs such that the potential for alcohol related “dose dumping” is avoided. The aim of this investigation was to assess the influence of ethanol on release of aspirin from hydrophilic matrix tablets. Tablets, comprising 149.5 mg Hypromellose (Methocel 2208, K4M; Dow Chemicals Co., USA), 149.5 mg aspirin (acetyl salicylic acid; Sigma Aldrich, UK) and 1 mg magnesium stearate (BDH, UK) were prepared by direct compression on a Manesty F3 single punch tablet press fitted with 8.95 mm diameter, flat punches. Tablets were obtained at crushing strengths (Dr Schleuniger 6D tablet tester) of 5.5–6 kP. Drug release experiments were carried out using B.P. Apparatus 1 at rotation speed 50 rpm in 500 ml of medium at 37°C. Media comprised 500 ml of acetate buffer (B.P.) with 0, 10, 20, 30 and 40% v/v ethanol. For each medium, 6 tablets were tested and drug release was monitored spectrophotometrically at 265 nm. With the exception of the medium containing 40% ethanol (medium v), profiles suggested near-zero order release. Release rates were proportional to the ethanol levels in the medium, although a “dose dumping” effect was not evident. Release profiles in medium (v) were characterized by an initial rapid release withrate progressively reducing over time, suggesting that a diffusion controlled release mechanism predominated. The high standard deviation for the 40% ethanol datacould be indicative of non-uniform gel layer generation causing inconsistency in release. This study has shown that hydroethanolic media can affect the kinetics and mechanism of drug release from matrixbased controlled release formulations in a manner related to the ethanol content and has highlighted the need for further investigation in this area.
The influence of alcohol on aspirin release from hypromellose matrix tablets
CESPI, MARCO;
2006-01-01
Abstract
The potential impact of concomitant alcohol consumption on in vivo release of drugs from modified release oral dosage forms is currently evincing much interest following the suspended marketing of Palladone (FDA Alert, July 2005). Human volunteer studies involving co-administration of drug and significant amounts of alcoholic beverages pose ethical and operational challenges. Consequently, in vitro studies, providing insight on release mechanisms in hydro-ethanolic media could guide formulation programs such that the potential for alcohol related “dose dumping” is avoided. The aim of this investigation was to assess the influence of ethanol on release of aspirin from hydrophilic matrix tablets. Tablets, comprising 149.5 mg Hypromellose (Methocel 2208, K4M; Dow Chemicals Co., USA), 149.5 mg aspirin (acetyl salicylic acid; Sigma Aldrich, UK) and 1 mg magnesium stearate (BDH, UK) were prepared by direct compression on a Manesty F3 single punch tablet press fitted with 8.95 mm diameter, flat punches. Tablets were obtained at crushing strengths (Dr Schleuniger 6D tablet tester) of 5.5–6 kP. Drug release experiments were carried out using B.P. Apparatus 1 at rotation speed 50 rpm in 500 ml of medium at 37°C. Media comprised 500 ml of acetate buffer (B.P.) with 0, 10, 20, 30 and 40% v/v ethanol. For each medium, 6 tablets were tested and drug release was monitored spectrophotometrically at 265 nm. With the exception of the medium containing 40% ethanol (medium v), profiles suggested near-zero order release. Release rates were proportional to the ethanol levels in the medium, although a “dose dumping” effect was not evident. Release profiles in medium (v) were characterized by an initial rapid release withrate progressively reducing over time, suggesting that a diffusion controlled release mechanism predominated. The high standard deviation for the 40% ethanol datacould be indicative of non-uniform gel layer generation causing inconsistency in release. This study has shown that hydroethanolic media can affect the kinetics and mechanism of drug release from matrixbased controlled release formulations in a manner related to the ethanol content and has highlighted the need for further investigation in this area.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
