DDR
DRUG DEVELOPMENT RESEARCH 75 : 68–75 (2014)
Research Article
Nimesulide/Methyl β-Cyclodextrin Inclusion Complexes: Physicochemical Characterization, Solubility, Dissolution, and Biological Studies Sayed H. Auda1,2* 1 Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia 2 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
Strategy, Management and Health Policy Enabling Technology, Genomics, Proteomics
Preclinical Research
Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics
Clinical Development Phases I-III Regulatory, Quality, Manufacturing
Postmarketing Phase IV
ABSTRACT Nimesulide (NIM) is an insoluble nonsteroidal anti-inflammatory drug (NSAID). Complexation of drug with methyl β-cyclodextrin was evaluated to improve solubility and dissolution rate of NIM. Complexation was achieved via a coevaporation technique to obtain different drug to polymer molar ratios (1:1, 1:2, and 1:3). The physicochemical characterization of the systems using powder X-ray diffraction and infrared spectroscopy was carried out to understand the influence of this technological process on the physical status of single components and complex systems and to detect possible interactions between drug and carrier. Moreover, quantitative solubility and in vitro dissolution studies of NIM alone and NIM inclusion complexes were studied in the dissolution media of phosphate buffer pH 5.5 and 7.4. The analysis provided existence of a molecular interaction between drug and carrier together in the complex state. The study showed that the inclusion systems enhanced of drug solubility, dissolution rate, and anti-inflammatory activity. Drug Dev Res 75 : 68–75, 2014. © 2013 Wiley Periodicals, Inc. Key words: nimesulide; β-cyclodextrin; formulation; anti-inflammatory effects
INTRODUCTION
Nimesulide (NIM) is a weakly acidic nonsteroidal anti-inflammatory drug (NSAID). It differs from other NSAIDs in that it contains a sulfonanilide moiety as the acidic group rather than a carboxylic one [Davis and Brogden, 1994] (Fig. 1). Like many NSAIDs, NIM is sparingly soluble in water (
DRUG DEVELOPMENT RESEARCH 75 : 68–75 (2014)
Research Article
Nimesulide/Methyl β-Cyclodextrin Inclusion Complexes: Physicochemical Characterization, Solubility, Dissolution, and Biological Studies Sayed H. Auda1,2* 1 Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia 2 Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
Strategy, Management and Health Policy Enabling Technology, Genomics, Proteomics
Preclinical Research
Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics
Clinical Development Phases I-III Regulatory, Quality, Manufacturing
Postmarketing Phase IV
ABSTRACT Nimesulide (NIM) is an insoluble nonsteroidal anti-inflammatory drug (NSAID). Complexation of drug with methyl β-cyclodextrin was evaluated to improve solubility and dissolution rate of NIM. Complexation was achieved via a coevaporation technique to obtain different drug to polymer molar ratios (1:1, 1:2, and 1:3). The physicochemical characterization of the systems using powder X-ray diffraction and infrared spectroscopy was carried out to understand the influence of this technological process on the physical status of single components and complex systems and to detect possible interactions between drug and carrier. Moreover, quantitative solubility and in vitro dissolution studies of NIM alone and NIM inclusion complexes were studied in the dissolution media of phosphate buffer pH 5.5 and 7.4. The analysis provided existence of a molecular interaction between drug and carrier together in the complex state. The study showed that the inclusion systems enhanced of drug solubility, dissolution rate, and anti-inflammatory activity. Drug Dev Res 75 : 68–75, 2014. © 2013 Wiley Periodicals, Inc. Key words: nimesulide; β-cyclodextrin; formulation; anti-inflammatory effects
INTRODUCTION
Nimesulide (NIM) is a weakly acidic nonsteroidal anti-inflammatory drug (NSAID). It differs from other NSAIDs in that it contains a sulfonanilide moiety as the acidic group rather than a carboxylic one [Davis and Brogden, 1994] (Fig. 1). Like many NSAIDs, NIM is sparingly soluble in water (
