Design of Sublingual Recombinant Human Insulin Drug Delivery System by Bio-Informatics

Abstract:
Background: Diabetes mellitus is a heterogeneous group of syndromes characterized by elevation of fasting blood glucose
that is caused by a relative or absolute deficiency in insulin. Diabetes is the leading cause of amputation and adult
blindness and a major cause of nerve damage, renal failure, heart attacks and stroke. Exogenous insulin is essential for the
management of Diabetes mellitus type 1 and has an adjunct role in the management of type 2 diabetes mellitus in which
oral hypoglycemic medicines display the leading management role. Pain, Lipodystrophy at the injection site, Nerve
damage, Thermolabile and microbial contamination during injection are the principal adverse effects of insulin
administered via IV or SC routes.
Aim of the study: Production and screening of sublingual recombinant human insulin drug delivery system.
Methodology: Type of the study: Screening experimental study. Micronization process like Jet or bead milling was
utilized to make micronized particles of recombinant human insulin less than 50 micron which resulted in more drug
solubility and better absorption through biological and physiological membranes of human body. This resulted in better
bioavailbility of the drug. In our study, micronized Insulin sublingual tablets were designed which were able to avoid the
hepatic first pass effect and gastrointestinal degradation. The sublingual tablets were prepared by direct compression
technique utilizing different concentrations of starch 1500 and microcrystalline cellulose. DSC and FTIR spectroscopy
were utilized in the drug and the polymer compatibility studies. Evaluation of preformulation properties of active
principal ingredient(API) was performed. As well postcompressional parameters as wetting time, disintegration time, in
vivo bio-availability, in vitro drug release, water absorption ratio study of the optimized formulation were assessed.
Results: The disintegration time of the optimized formulation was up to 45 seconds. The in vitro release of insulin from
optimized sublingual tablets was found to be up to 15 minutes. The percentage relative bioavaiability of insulin from
optimized sublingual tablets was 81%.
The precompression parameters were within an acceptable range of pharmacopoeia specifications. No possible interactions
were noticed between the drug and the polymer via FTIR spectroscopy and DSC study.
Discussion: The sublingual tablet of insulin was tested on animal models, evaluated in human clinical trials phases 1/2
and compared with standard regular soluble insulin injection formulations for efficacy. The sublingual formulation of
insulin showed high bio-availability and efficacy .
Conclusion: The sublingual tablets of recombinant human insulin helped to overcome the disadvantages of subcutaneous
injections of insulin.