Comparison of the effect of tromethamine and polyvinylpyrrolidone on dissolution properties and analgesic effect of nimesulide

Abstract

The solubilizing and absorption enhancer properties towards nimesulide (ND) of tromethamine (Tris) and polyvinylpyrrolidone (PVP) have been investigated. Solid binary systems were prepared at various drug-polymer ratios by mixing or coprecipitation, characterized by differential scanning calorimetry, X-ray diffractometry, and Fourier transform infrared spectroscopy, and tested for dissolution behavior. Both carriers improved drug dissolution and their performance depended on concentration of the hydrophilic carrier in coprecipitates. Tris was more effective than PVP, despite the amorphizing power of PVP as revealed by solid state analyses. Complete drug amorphiztion was attained at 1:3 (wt/wt) drug:PVP, 25% (wt/ wt) ND in PVP. According to thermal behavior of ND and Tris, ND-Tris systems present a eutectic behavior. The eutectic composition was 30% ND-70% Tris at~129°C. Amorphous ND-PVP and eutectic ND-Tris mixtures showed an improvement of 5.55 and 6.6 times of drug dissolution efficiency, respectively. In vivo experiments in mice demonstrated that administration of 50 mg/kg of drug coprecipitated with PVP or Tris resulted, respectively, in a 50% and 94% reduction of acetic acid-induced writhings in comparison with pure drug, which, instead, was statistically ineffective as compared with the control group. Moreover, the eutectic mixture of ND-Tris demonstrated antiwrithing potency 1.88 times higher than amorphous ND-PVP coprecipitate. Thus, the solubilizing power, dissolution-enhancing effect, and analgesic effect enhancer ability toward the drug make Tris particularly suitable for developing a reduced-dose, fast-release solid oral dosage form of nimesulide.

Improvement of Dissolution and Hypoglycemic Efficacy of Glimepiride by Different Carriers

“…Thus, more contact may be allowed resulting in an interaction that could not occur in their solid PMs and was not seen in their FTIR results. The possibilty of conversion of some crystalline compounds into highly dispersed state due to the thermal energy supplied during DSC scan has been reported in other studies (5,32). Excess Tris without interaction during DSC scan may account for the presence of the two peaks (141°C Fig.…”

“…Tris showed highest solubilizing efficiency and binding affinity followed by PVP-K25 then LM-CH as clarified by the slope and K s values, respectively, of the corresponding linear curves (Table II). Being compratively strong basic, Tris may be expected to form more stabilized complexes with Gmp, hence higher solubility of this drug was observed (5,7,13). The hydrogen bonding of PVP with Gmp as suggested by FTIR results might stabilize the complex with this drug (Fig.…”

“…GMs were prepared by grinding the corresponding PM in vibrational mill for 1 h (Microne Micronising Mill, England). The Coppts were prepared by the solvent evaporation technique (5,20). The solvent was methanol and evaporation was under vacuum at 40°C.…”

“…1b, c, and d respectively) have been widely used for this purpose. For example, different solid binary systems as physical mixtures (PMs) and coprecipitates (Coppts) with Tris and PVP were successful in increasing the dissolution and the analgesic effect of nimesulide (5). Dissolution rates of benzoic acid (6), hydrochlorothiazide (7), and furosemide (8) were markedly enhanced by use of Tris as a carrier.…”

Pharmaceutical development of co-crystals

“…On average, the best exposure, at both doses, was reached with the fumaric acid cocrystal containing formulation (F8) [3,73,74]. The measured AUC results were promising with the partially amorphous base containing formulation (F7) [75] as well but because of a scalability issue and the decrease in terms of exposure at higher dosage, the co-crystal containing formulation got the first priority. The targeted exposure was reached with the citric acid containing formulation as well (F6) however it was kept as a back-up option based on the complexity of the formulation for toxicological studies.…”