• Kushagra Khanna, Ritu Karwasra, Sandeep Choudhary, Deeksha Sharma, Nitin Sharma, Puja Nagpal, Varsha Chorsiya, Dhruv Kumar Nishad, Harvinder Popli, and Aseem Bhatnagar.
• Department of CEPIN, Institute of Nuclear Medicine and Allied Sciences (INMAS) Defence Research and Development Organization, Ministry of Defence, Govt. of India, Timarpur, Delhi, 110054, INDIA; Department of Pharmacy, Delhi Pharmaceutical Sciences and Research University, New Delhi, 110017, INDIA.
• Injury. 2020 Sep 1; 51 (9): 1970-1978.

BackgroundNalbuphine (NLB) is a kappa-agonist and mu-partial antagonist, widely used for opioid withdrawal de-addiction, opioid-induced pruritis and as emergent analgesia.ObjectiveThe present study aimed to assess the safety and efficacy of NLB in pain sensitization, through a submental route so as to provide faster management in emergent situations.Materials & MethodsIn-vivo efficacy and safety studies of NLB-submental injection were assessed in Sprague-Dawley(SD) rats. For eddy's hot plate study, animals were allocated into three groups, the first group served as normal control; group II received NLB (through submental route at 1.2 mg/kg); group III received NLB (through intramuscular route at 1.2 mg/kg). Response latency (in terms of response latency) was measured at 10, 30 & 60 min in all the experimental groups. Safety studies were carried out according to OECD 423. In-vitro release study was conducted using a cellulose dialysis membrane (12,000 KDa). The biodistribution and release kinetics studies were carried out using gamma scintigraphy studies in New Zealand rabbits and humans respectively.ResultsThe response latency of NLB from the submental route was found to be 7.17 (SD 1.47) seconds and in the case of the intramuscular route it was calculated as 4.00 (SD 1.26) seconds at 10 min. The data depicts the better efficacy of submental injection in ameliorating pain than the intramuscular injection. Toxicity studies predict the safe profile through a submental route. The release kinetics in humans of submental NLB was 46% faster as compared to the intramuscular site of injection. The NLB injection through both routes was compared by non-invasive gamma scintigraphy technique and we found that submental injection has faster (within 10 min) onset of action & distributes rapidly.ConclusionThe submental route of NLB is faster, more efficacious than the intramuscular route. Thus, we conclude that in the case of emergent scenarios (i.v or i.m. route is compromised), where immediate relief is necessary, the submental route is a preferred choice.Copyright © 2020 Elsevier Ltd. All rights reserved.

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