Influence of Manufacturing Parameters on Development of Contraceptive Steroid Loaded Injectable Microspheres

Abstract

The main objective of this work was to develop a system consisting of polymeric microspheres loaded with steroid drugs. The drugs were encapsulated using biodegradable poly(lactide-co-glycolide) (PLG) and poly(e ecaprolactone) (PCL) by double emulsion solvent evaporation method. The lipophilic drugs, levonorgestrel and ethinylestradiol were made soluble by adding ethanol/water mixture. The effects of parameters like polymer concentration and stabilizer concentration were studied on the size, size distribution, surface properties and loading efficiencies of microspheres. The formulated microspheres were smooth, spherical and uniform in shape and size. Fourier transformed infrared spectroscopy and differential scanning calorimetry studies seemed to confirm the absence of chemical interaction between the drugs and the polymers, while the drugs were dispersed in the polymer. The increase in polymer concentrations increased the size as well as the loading efficiency of microspheres. Data obtained in this study demonstrated that the PLG/PCL microspheres may be a suitable polymeric carrier for long acting injectable drug delivery.

Controlled release of drugs from multi-component biomaterials

“…Due to its slow degradation [13][14][15], high permeability to many drugs and low toxicity [16], PCL microcarriers consisting of a drug dispersed in spherical polymer matrix have been extensively evaluated for the administration of active compounds over long periods [17][18][19][20]. In these systems, the drug release is governed by factors depending on the polymer (molecular weight, crystallinity), the drug (solubility in water/biological fluids) and their interactions, as well as on the microcarrier's characteristics (drug loading, particle size, porosity) [21].…”

Characterization of polymeric poly(ϵ‐caprolactone) injectable implant delivery system for the controlled delivery of contraceptive steroids

“…The microspheres were prepared by a w/o/w emulsification–solvent evaporation method as described earlier by us 25, 26. Briefly, a saturated solution of LNG (15 mg) and EE (3 mg) were taken in the ratio of 1:5 in an ethanol:water mixture (7:3) and was emulsified at 4000 rpm for 10 min using a Remi propeller mixer into 10 mL dichloromethane containing 180 mg of polymer.…”

“…In our earlier work we have shown that PCL acts as an excellent carrier for contraceptive hormone release 25, 26. The objectives of our work were to entrap both levonorgestrel (LNG) and ethinyl estradiol (EE) within biodegradable microspheres by the w/o/w method and characterize the system with a view of drug content, surface morphology, in vitro degradation, in vitro and in vivo drug release studies.…”

Long-Acting Injectable Hormonal Dosage Forms for Contraception

“…NET microcrystals were successfully encapsulated into PLA and PLGA microspheres by suspending the NET microcrystals in polymer acetone/chloroform co-solvent solutions followed by adding this suspension into 5 wt% polyvinyl alcohol (PVA) solution to construct the o/w emulsion, and then solvent evaporation. Afterwards, PLGA became the most popular polymer for fabricating microspheres to encapsulate contraceptive APIs including LNG, gestodene and ethinyl estradiol using o/w or w/o/w emulsion/solvent evaporation technique (20)(21)(22)(23)25,27,50,51). Poly(ε-caprolactone) (PCL) is a second popular polymer for fabricating microspheres to encapsulate contraceptive APIs including LNG, ethinylestradiol, norgestrel, progesterone and β-estradiol using o/w or w/o/w emulsion/solvent evaporation technique (49,(52)(53)(54)(55)(56).…”