Development and Evaluation of Vasoactive Intestinal Peptide Freeze-Dried Injection

Abstract

Introduction: Vasoactive intestinal peptide (VIP), a ubiquitous, naturally synthesized human peptide is extensively documented to have diverse physiological effects like anti-inflammatory, immune-modulatory, anti-hypertensive, stimulation of contractility in the heart, vasodilation, and promoting neuroendocrine-immune communication. The synthetic form of VIP is called aviptadil (AVP). The main objective of this research was to develop a novel stable lyophilized dosage of VIP (Aviptadil) using sucrose as a bulking agent. AVP is a peptide with known concern for aqueous stability, which seems to be challenging for storing finished drug products and supply chain management. The VIP injection was developed using the lyophilization technique in the presence of bulking agent and some other pH-adjusting agent. The bulking agent and solvent system selection depends upon the solubility, stability of the drug substance, and feasibility during manufacturing. During product formulation development, the bulk solution was evaluated for processing time and temperature impact. The lyophilization cycle was developed using the most advanced freeze-drying technology. Result and discussion: With the usage of bulking agent (sucrose) as may act as a cryoprotectant for peptide, the formulated bulk solution was freeze-dried, and primary drying was done at-25°C (below than critical product temperature) followed by secondary drying at 25°C. The critical quality attributes of lyophilized drug products like the description of lyophilized cake/powder, moisture content, reconstitution time, active drug content and color of the solution were evaluated. The developed formulation bulk solution was stable and compatible with contact materials like SS vessels when hold up to 24 hours at 2 to 8°C. The optimized freeze-dried product meets the predefined acceptance criteria as part of the quality target product profile. Conclusions: It can be concluded from the research work carried out that a stable lyophilized parenteral formulation containing VIP (AVP) was developed using sucrose as a bulking agent. These findings show that the freeze-dried formulation is an appropriate technological remedy for stabilizing VIP in lyophilized injectable dosage form.