Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1997-05-15
1998-12-29
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514570, A61K 31715, A61K 3119
Patent
active
058542264
DESCRIPTION:
BRIEF SUMMARY
This application is the national phase of international application PCT/GB95/02679, filed Nov. 14,1997 which was designated the U.S.
BACKGROUND OF THE INVENTION
This invention relates to a pharmaceutical composition for oral administration comprising an inclusion complex of a non-steroidal anti-inflammatory drug (NSAID) and a cyclodextrin, and an alkali agent.
Oral treatment with non-steroidal anti-inflammatory drugs has the disadvantage of gastrointestinal side effects, particularly local gastric irritation. Contact between the NSAID and the mucosa is believed to constitute an important factor in the pathogenesis of gastric irritation important in peptic ulceration? Alimentary Pharmacology and Therapeutics 1987, 1, 5405-5475!. Commercial preparations of NSAID's for oral administration include enteric coated tablets which release the drug in the duodenum so as to avoid local gastric irritation. This however has the disadvantage that peak plasma levels of the drug are reached between one to four hours after administration of the enteric coated tablets.
An example of an NSAID is diclofenac which is a phenylacetic acid NSAID with potent anti-inflammatory and analgesic actions highly utilized in the treatment of acute and chronic pain especially when associated with inflammation e.g. post operative pain, rheumatism, arthritis, gout, musculo-skeletal injury and trauma. In order to reduce the lag-time associated with enteric coated diclofenac tablets, a non-enteric coated tablet and dispersible dosage form have recently been commercialized with indications for short-term treatment of acute inflammatory conditions, although gastro-intestinal side effects are frequent, particularly local
There is therefore a need for oral pharmaceutical compositions of NSAIDs e.g. diclofenac, which provide rapid absorption with minimized gastrointestinal irritation.
The properties of cyclodextrins and numerous inclusion complexes are well Technology (1988) Kluwer Academic Publishers, Dordrecht!.
Depending on solvent conditions, a dissolved inclusion complex exists in equilibrium between uncomplexed host and guest and complexed host/guest. Orally administered cyclodextrin-drug inclusion complexes generally result in rapid absorption of the drug, facilitated by the cyclodextrin, whereas the cyclodextrin is not absorbed to any significant extent. Additionally cyclodextrin inclusion complexes of certain drugs have been shown to Cyclodextrins in Pharmacy (1994), Kluwer Academic Publishers!. Cyclodextrins therefore possess ideal properties as drug carriers. Cyclodextrins and their inclusion complexes possess favourable flow, binding and compaction properties facilitating tablet compression.
The diffusability of a diclofenac (acid) complex with beta cyclodextrin has Complexes, Orienti, I., Cavallari, C. and Zecchi, V. Arch. Pharm (Weinheim) 1989, 322, 207-211!. The complex was found to be poorly soluble at pH 2.
The effect of addition of buffering agents to tablet and capsule formulations of sparingly soluble acidic drugs e.g. furosemide, is known F. & van der Watt J. G. Relationship between the pH of the diffusion layer and the dissolution rate of furosemide; Drug Development and Industrial Pharmacy 1991, 17, 1715-1720!.
South African Patent No 94/5930 in the name of Smithkline Beecham PLC discloses a pharmaceutical composition for oral consumption in aqueous solution comprising a drug/beta-cyclodextrin complex, wherein the composition further comprises a pharmaceutically acceptable acid-base couple, in a quantity sufficient to cause the drug/beta-cyclodextrin complex to dissolve when the composition is mixed with cold water and provide a solution with acid or neutral pH. It is essential to this pharmaceutical composition that it contain the combination of an acid and a base couple, which may or may not be effervescent.
SUMMARY OF THE INVENTION
According to the invention there is provided a pharmaceutical composition for oral administration comprising an inclusion complex of a non-steroidal anti-inflammatory drug or a pharmaceutic
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Glintenkamp Lueta A
Nicholson Douglas G M
Penkler Lawrence J
Van Oudtshoorn Michiel C B
Farmarc Nederland BV
Henley III Raymond
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