The influence of concomitant use of alcoholic beverages on hypromellose matrix tablets

Dec 01, 2008


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People have consumed alcoholic drinks for thousands of years and this tradition continues to occupy an important place in many cultures. According to a survey in 2002,1 7–28% of adults in the UK drink alcohol on five or more days a week. US statistical data indicates that a significant proportion of the American population also routinely consumes alcoholic beverages.2

The UK survey shows that older people drink alcohol more frequently than younger people: 21% of men and 11% of women aged 65 years and over had consumed alcohol every day during the week prior to the survey, compared with only 4% of men and 2% of women aged 16–24 years for the same time period. As the prevalence of chronic conditions increase with age, the elderly also consume more drug prescriptions as a percentage of the population for treating cardiovascular, pain management, arthritis and central nervous system conditions. The elderly are also likely to consume more specialized dosage forms because of the continued trend towards extended release (ER) formulations.

These trends make it imperative to understand the impact of alcohol consumption on modified release or ER dosage forms.

HPMC

Hydrophilic matrix systems are a popular and widely used approach to extending drug release in tablets. Hypromellose (hydroxypropyl methylcellulose [HPMC]) is the most widely used rate-controlling polymer in these systems because of its safety, availability, global compliance and physicochemical/mechanical characteristics.3–6

Upon contact with aqueous media, HPMC polymer hydrates quickly to form a protective gel layer on the matrix surface. Soluble drugs are released primarily by diffusion through this gel layer while actives with low solubility are released primarily by gel erosion. Drug release typically occurs through a combination of these two mechanisms.7,8 Rapid polymer hydration and uniform gel formation are critical to the integrity and subsequent performance of HPMC matrix systems.

Drug release rate from HPMC ER tablets depends on many factors including:

  • polymer type and level9
  • drug solubility and dose10,11
  • polymer/drug ratio12
  • filler type and level13
  • polymer/filler ratio14
  • particle size of drug and polymer15
  • porosity and shape of the matrix.6

Drug release rate may also be significantly affected by the medium parameters to which the matrix is exposed, prior to, or upon ingestion, including pH, electrolytes, surfactants and enzymes.16–23

Taking into account the impact of dissolution medium on gel formation and, therefore, drug release from HPMC matrices, the influence of hydro-alcoholic media for cases when the dosage may be taken with, shortly before or after an alcoholic drink has been recently investigated in a number of studies.

Dose dumping

Accidental poisoning with ER dosage forms, although infrequent, poses special treatment problems that are often not seen with immediate release medication, as failure of an ER product can subject the body to a toxic drug level. Any unintended release of the total or a significant fraction of the active substance from an ER dosage form during a short period of time is referred to as 'dose dumping'.


On the go...
The likelihood of dose dumping for certain ER products when administered with food has been investigated previously,24–27 and FDA has also issued a report to address the issue.28 However, some limited in vivo studies conducted in the 1980s showed that pharmacokinetics and the release properties of ER dosage forms were not influenced by alcohol.29