Technical Note: The Effect of Alcoholic Beverages on Sustained Release - Pharmaceutical Technology

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Technical Note: The Effect of Alcoholic Beverages on Sustained Release
The authors evaluated the effect of alcoholic beverages on the release profiles of sustained-release dosage forms containing metformin and diclofenac.


Pharmaceutical Technology
Volume 34, Issue 12, pp. 47-49

Methods

Metformin. The dissolution study for both metformin formulations was carried out with 900 mL of demineralized water (maintained at 37 0.5 C) in a US Pharmacopeia Type I dissolution apparatus at 100 rpm. The tablets were used as received. Six tablets from the same batch of each product were tested. A suitable volume of medium was withdrawn, filtered, and diluted with demineralized water, and the amount of metformin released from the dosage form was determined using a UV–vis spectrophotometer (Model No.1700 E, Shimadzu, Kyoto) at a wavelength of 233 nm.

For the alcoholic dissolution study, the designated volume of alcoholic beverages was included in medium for 1 h (the volume was increased to 900 mL using demineralized water) to simulate in vivo conditions. After 1 h, the medium was replaced with the fresh demineralized water at 37 0.5 C. The same procedure was followed for the determination of drug release in all solutions.

The designated volumes of various alcoholic beverages were the following:
  • Kingfisher Strong beer: 500 mL
  • Kingfisher Mild beer: 500 mL
  • Rum: 60 mL
  • 40% alcohol: 15 mL.

The data obtained were analyzed using software (PCP-DISSO, Bharati Vidyapeeth College of Pharmacy, Pune, Maharashtra, India).

Diclofenac. The dissolution study for both diclofenac formulation was carried out with 900 mL of demineralized water (maintained at 37 0.5 C) in a USP Type I dissolution apparatus. The apparatus ran at 50 rpm for instant-release diclofenac and at 100 rpm for sustained-release diclofenac.

The tablets were used as received. Six tablets from the same batch of each product were tested. The amount of diclofenac released from the dosage form was determined using a UV–vis spectrophotometer (Model No.1700 E, Shimadzu) at a wavelength of 277 nm.

For the alcoholic dissolution study, the designated volume of alcoholic beverages was included in medium for 1 h (the volume was increased to 900 mL using demineralized water) to simulate in vivo conditions. After 1 h, the medium was replaced with the fresh demineralized water at 37 0.5 C. The same procedure was followed for the determination of drug release.


Figure 1: Drug-release profile of instant-release metformin formulation over time in the presence of various alcoholic beverages.
The designated volumes of various alcoholic beverages were the same as for the metformin study. The data obtained were analyzed using PCP-DISSO software.

Results and discussion


Figure 2: Drug-release profile of instant-release diclofenac formulation over time in the presence of various alcoholic beverages.
The release of drug from instant-release metformin tablets depended on the volume of alcoholic beverage present. Drug release was fastest in Kingfisher Strong beer. Release was progressively slower in Mild beer, rum, and 40% alcohol. The release was slowest in water (see Figure 1). Both the strength and the volume of the alcoholic beverage affected the release rate. A similar trend was observed for instant-release diclofenac tablets (see Figure 2). Thus, the authors concluded that the volume and strength of the alcoholic beverage affected that drug's release as well.


Figure 3: Drug-release profile of sustained-release metformin formulation over time in the presence of various alcoholic beverages.
The release of sustained-release metformin was similar in 40% alcohol and rum. Drug release was slower in the Strong and Mild beers and slowest in water (see Figure 3). These results indicate that the drug release was affected by the strength of the alcoholic beverages rather than by their total volume. This conclusion suggests that drug release is strongly influenced by alcohol's ability to disrupt the sustained-release mechanism. The similar release profiles obtained for the sustained-release diclofenac formulation confirmed this proposition (see Figure 4).


Figure 4: Drug-release profile of sustained-release diclofenac formulation over time in the presence of various alcoholic beverages.
The consequences of the changes in the dissolution profiles observed in sustained-release formulations depend on the drug. Dose dumping of metformin could result in anaphylactic reactions and lactic acidosis, among other effects. In addition, metformin is excreted unchanged by the renal route. Therefore, dose dumping of metformin also could result in renal impairment. Dose dumping of diclofenac could cause allergic reactions, fluid retention, and impairment of renal function (4).


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