Stabilization of luteinizing hormone-releasing hormone in a dry powder formulation and its bioactivity

Background: Luteinizing hormone-releasing hormone (LHRH) is a naturally occurring hormone that controls sex hormones in both men and women. In general, LHRH is poorly absorbed through the gastrointestinal tract due to its large molecular size, high polarity, and loss from enzymatic degradation.

Objective: Prepare and develop LHRH in a dry power formulation with stability and biological activity.

Methods: Mannitol (M) and glycine (G) were chosen as ingredients to stabilize and protect LHRH during the freeze drying processes and during storage. The physicochemical properties of LHRH dry powders were examined by capillary electrophoresis, fluorescence spectrophotometry, scanning electron microscopy, and photon correlation spectroscopy. The release of LHRH from the dry powder was carried out in dissolution apparatus. In addition, a rat model was employed to study the bioactivity of LHRH in the dry powder form.

Results: The LHRH dry powder formulations using M and G in the ratios of 6:4 and 7:3 were more stable than other formulations. LHRH colloids containing M:G showed no aggregation after storage at 4°C for one month. The concentration of LHRH in the dry powder form was more stable than that of LHRH in solution form. All the LHRH dry powder formulations were instantly dissolved within 10 seconds in an aqueous medium. After the LHRH dry powder (13 mg) was reconstituted and administered intraperitoneally to male rats during a one-month period, the testosterone level in the plasma was significantly decreased compared with an untreated group (15.0±1.0 ng/mL, 15.0±1.0 ng/mL and 20.0±2.0 ng/mL for LHRH containing M:G; 6:4, 7:3, and 8:2, respectively, compared to the control of 35±2 ng/mL, p<0.05).

Conclusion: The LHRH dry powder formulations had good physicochemical properties and bioactivity.