Development, Characterization and Evaluation of Parenteral Formulation of Diclofenac Sodium
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Research Article Development, Characterization and Evaluation of Parenteral Formulation of Diclofenac Sodium Neha Panchal,1 Manjot Kaur,1 Abhay Tharmatt,1 Shubham Thakur,1 and Subheet Kumar Jain1,2
Received 28 February 2020; accepted 8 June 2020 Abstract. Diclofenac sodium is a potent NSAID, classified under BCS class II category having a poor aqueous solubility. Recently, its injectable formulation got banned and withdrawn from the market due to its severe nephrotoxicity caused by the use of synthetic surfactant, i.e. Transcutol-P as solubilizer. Therefore, the present study was aimed to prepare Transcutol-P free injectable using Vitamin E TPGS as a biosurfactant which is in list of inactive ingredients by US-FDA. Various cost effective aqueous injectable formulations were prepared by mixed solvency method that were characterized and optimized for different in vitro quality control parameters. Further, ex vivo hemolytic study showed the increased safety (23.4 ± 1.6%) of optimized formulation as compared with its commercial counterpart (100 ± 4.2%) at 75 mg/ml. Furthermore, in vivo acute and sub-acute toxicity study demonstrated an increase in LD50 to 123.75 ± 6.2 mg/kg to that of a commercial counterpart (109.96 ± 5.5 mg/kg). In addition, optimized formulation demonstrated better mean residence time and area under curve when compared with commercial test group, respectively. Moreover, optimized formulation was also evaluated for its therapeutic efficacy. The results obtained from acetic acid-induced writhing test in albino mice showed 78 ± 2.1% protection from writhes after 120 min, whereas the commercial formulation had only 48.3 ± 1.9% protection. Additionally, carrageenan-induced rat paw edema model also confirmed the better anti-inflammatory activity of optimized aqueous injectable formulation than its commercial counterpart. Thus, the developed aqueous injectable formulation of diclofenac is free from toxic Transcutol-P with enhanced safety and therapeutic efficacy. KEY WORDS: biosurfactants; vitamin E TPGS; diclofenac; injectable; parenteral; Transcutol-P free.
INTRODUCTION Conventionally, about 40% of new chemical entities (NCEs) has to get developed into new formulations due to poor aqueous solubility established by pharmaceutical industry screening programs. The solubility issue convolutes the delivery of many drugs as it results in lesser bioavailability due to poor drug absorption (1). It is becoming one of the most researched topics in the developmental phase, so there are numerous techniques involving surfactants, co-solvents, self-emulsification, micelles and solid dispersion, etc. (2). These techniques till now are very helpful in providing better results and ultimately improving the human health. However, such developmental challenges lead to an increment in cost which is a big trouble for the patient’s pocket (3). From different solubility enhancement techniques, surfactants are achieving great attention as they are broadly used 1
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amri
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