Norethisterone contraceptive microspheres

Long-Acting Injectable Hormonal Dosage Forms for Contraception

“…On the other hand, PLA and PGA had lower permeability to steroidal drugs but undergo homogenous erosion, resulting in the release of LNG from the PCL matrix to be controlled mainly by erosion (64,67). It was also observed that PLGA microspheres degraded faster and NET was released from the microspheres faster when the amount of hydrophilic glycolide component was increased (27). The chirality of polymers, crosslinking density and drug loading of microspheres also play important roles in controlling contraceptive API release profiles.…”

“…In the initial attempts to develop contraceptive API-loaded microspheres, the conventional emulsion technique with simple stirring or high shear stirring was used to fabricate the microspheres (20)(21)(22)27,48,49,52,56,58,60). In these emulsion systems, the droplet formation reached a steady-state size equilibrium or size distribution due to continuous droplet collision, coalescence, and re-division.…”

“…Through extensive investigation over past several decades, it has been acknowledged that many factors of microspheres such as their chemical and physical structure (composition, chirality and crosslinking density), drug loading and distribution, physical property (size, shape, size distribution, and molecular weight), and fabrication and sterilization processes significantly affects drug release profiles including release rate, duration of action and initial burst, and microsphere overall performance in vitro, in animals, and in humans (20,23,27,(45)(46)(47)(48)(49)(50). In the following, we will discuss how these factors have been investigated for the development of microspheres as injectables for long-term 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).…”

“…Drug microcrystals have advantages of low cost due to less process steps and materials involved, and using water as an administration vehicle, but needs reconstitution and are difficult to achieve sustained release of APIs for more than 3 months. Microspheres have the advantages of using water as a vehicle, and capability of achieving more than 3 month release of APIs due to the retarding effect of polymeric matrix (4,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). However, they need reconstitution and some toxic organic solvents used in the fabrication of microspheres might be trapped inside and the manufacturing is generally costly for well-defined microspheres.…”