Novel Self-micro Emulsifying Drug Delivery System for Safe Intramuscular Delivery with Improved Pharmacodynamics and Pharmacokinetics.

Subheet Kumar Jain, Neha Panchal, Amrinder Singh, Shubham Thakur, Navid Reza Shahtaghi, Surbhi Sharma, Akshay Guleria

Current drug delivery 2021

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Diclofenac Sodium (DS) injection is widely used in the management of acute or chronic pain and inflammatory diseases. It incorporates 20% w/v Transcutol-P as a solubilizer to make the stable injectable formulation. However, the use of Transcutol-P in high concentration leads to adverse effects such as severe nephrotoxicity, etc. Some advancements have resulted in the formulation of an aqueous-based injectable but that too used benzyl alcohol which is reported to be toxic for human use. This study aimed to develop an injectable Self-Micro Emulsifying Drug Delivery System (SMEDDS) as a novel carrier of DS for prompt release with better safety and efficacy. A solubility study was performed with different surfactants and co-surfactants. The conventional stirring method was employed for the formulation of SMEDDS. Detailed in vitro characterization was done for different quality control parameters. In vivo studies were performed using Wistar rats for pharmacokinetic evaluation, toxicological analysis, and analgesic activity. The optimized formulation exhibited good physical stability, ideal globule size (156±0.4 nm), quick release, better therapeutics, and safety, increase in LD50 (221.9 mg/kg) to that of the commercial counterpart (109.9 mg/kg). Furthermore, pre-treatment with optimized formulation reduced the carrageenan-induced rat paw oedema by 88±1.2% after 4 h, compared to 77±1.6% inhibition with commercial DS formulation. Moreover, optimized formulation significantly (p<0.05) inhibited the pain sensation in the acetic-acid induced writhing test in mice compared to its commercial equivalent with a better pharmacokinetic profile. The above findings confirmed that liquid SMEDDS can be a successful carrier for the safe and effective delivery of DS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Citation

Subheet Kumar Jain, Neha Panchal, Amrinder Singh, Shubham Thakur, Navid Reza Shahtaghi, Surbhi Sharma, Akshay Guleria. Novel Self-micro Emulsifying Drug Delivery System for Safe Intramuscular Delivery with Improved Pharmacodynamics and Pharmacokinetics. Current drug delivery. 2021;18(10):1533-1549