INDUSTRIALIZATION OF MEDROXY PROGESTERONE ACETATE IN PROLONGED PARENTAL SUSPENSION (PART I)
Keywords:
Medroxy progesterone acetate (MPA), L-cysteine, Sodium metabisulfateAbstract
Objective: Medroxy progesterone acetate (MPA) is structurally related to progesterone it is given by mouth or by intramuscular (IM) as a contraceptive in an aqueous suspension injection. It was reported that the MPA suspension was chemically and physically unstable due to a reaction between the different excipients. Evaluate the effect of different antioxidants as L-cysteine, ascorbic acid, sodium metabisulfate and D-L methionine (DLM) on the stability of MPA in suspension formula, as well as comparative studies was conducted to evaluate the most promising formula with the marketed product. On the other hand, the thermal and photo-stability study for the selected formula was done to determine the conditions of storage on the product formula.
Methods: Four preparations were prepared by adding either DLM (0.15 gm %), ascorbic acid (0.03 gm %), sodium metabisulfate (SMBS) (0.25 gm) or combination of SMBS with ascorbic acid as an antioxidant, all ingredients we mixed together using (Heidolph) homogenize
Results: Indicate that, the formula contains 0.3 gm of polysorbate 80, PVP, paraben ester and 0.13 gm % phosphate buffer with DLM or ascorbic acid as an antioxidant revealed acceptable pH stability which was studied by FT-IR, X-ray diffraction and particle size analysis.
Conclusion: Formula with DLM (F-DLM) showed good rheological behavior. Thermal degradation of the suspension formula with ascorbic acid (F-ascorbic acid) or DLM revealed acceptable shelf life for more than 4 years for F-DLM and about 2 years for the F-ascorbic acid while the two formulae exhibited dramatic photo degradation under UV lamp of the 3 month study
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