No abstract

Nonsteroidal antiinflammatory drugs are widely used in modem medicine for the treatment of various disorders. A special place in this group belongs to ibuprofen, which has been used since 1969 and is recognized as an effective low-toxicity analgesic.At the same time, ibuprofen is not free of disadvantages inherent in all drugs capable of inhibiting the cytoprotective isoenzyme cyclooxygenase. The main drawbacks are a decrease in the level of prostaglandins in the mucous membranes of the gastrointestinal tract and the related ulceration effect, which is especially pronounced in the case of prolonged administration of these nonsteroidal antiinflammatory drugs [ 1,2].Since ibuprofen is available without special prescriptions and can be used by patients for a long time without regulation, medicinal forms of this drug must be developed so as to exhibit minimum side effects [3].There are several commonly accepted methods used by 9 modem pharmacy in order to reduce the irritating action of drugs. This goal is mostly achieved by using supplementary components improving the solubility of the drugs or restricting the area of contact between drug and mucous membrane. Various high-molecular-weight compounds (polymers) are among these substances.The purpose of this work was to study the interaction of ibuprofen with various polymers and select substances providing a maximum decrease in the irritating effect of this drug. EXPERIMENTAL PARTThe experiments were performed with commercial ibuprofen (Agio Pharma, India) meeting all requirements of the US State Pharmacopoeia (XXIII ED.). The group of polymers included 13-eyclodextrin (~-CD), poly(ethylene oxide) (PEO) with a molecular weight of M=1500 (PEO-1500), low-molecular-weight poly(vinyl pyrrolidone) t Pyatigorsk State Pharmaceutical Academy, Pyatigorsk, Russia. 604(PVP) with M = 12600, low-molecular-weight poly(vinyl alcohol) (PVA), and water-soluble methyl cellulose (MC) (commercial MTs-35 grade).The extent of interaction between ibuprofen and polymers was studied by methods of viscometry, spectrophotometry, and thermal analysis.The effect of polymers on the solubility of ibuprofen in water was studied in a series of experiments, whereby 200 mg aliquots of ibuprofen were introduced into 100 ml volumes of polymer solutions with various concentrations (from 0.2 to 20 mg/ml at an 0.2 mg/ml step) in 250-ml flasks. Then the flasks were shaken for 1 h, allowed to stand for 24 h, and shaken for 1 h again. In parallel, a control test was performed with ibuprofen in water. Each experiment was conducted in five independent runs. Upon final equilibration, the solutions were filtered and the concentration of ibuprofen in each filtrate was determined by spectrophotometry at ~. = 262 nm (E = 21.2). The averaged results of these experiments are presented in Fig. 1. As seen from these data, the solubility of ibuprofen in water is 0.37 mg/ml. Among the polymers studied, only PEO did not change to any significant extent the solubility of ibuprofen in water.PVP exhibited a weak solubilizing e...