Preparation of TPP-crosslinked chitosan microparticles by spray drying for the controlled delivery of progesterone intended for estrus synchronization in cattle

HELBLING, IGNACIO M.; BUSATTO, CARLOS A.; FIORAMONTI, SILVANA A.; PESOA, JUAN I.; SANTIAGO, LILIANA; ESTENOZ, DIANA A.; LUNA, JULIO A.

PHARMACEUTICAL RESEARCH

SPRINGER/PLENUM PUBLISHERS

Año: 2018 vol. 35

0724-8741

Purpose: Planned reproduction in cattle involves regulation of estrous cycle and the use of artificial insemination. Cycle control includes the administration of exogenous progesterone during 5?8 days in a controlled manner allowing females to synchronize their ovulation. Several progesterone delivery systems are commercially available but they have several drawbacks. The aim of the present contribution was to evaluate chitosan microparticles entrapping progesterone as an alternative system. Methods: Microparticles were prepared by spray drying. The effect of formulation parameters and experimental conditions on particle features and delivery was studied. A mathematical model to predict progesterone plasma concentration in animals was developed and validated with experimental data. Results: Microparticle size was not affected by formulation parameters but sphericity enhances as Tween 80 content increases and it impairs as TPP content rises. Z potential decreases as phosphate content rises. Particles remain stable in acidic solution but the addition of surfactant is required to stabilize dispersions in neutral medium. Encapsulation efficiencies was 69?75%. In vitro delivery studies showed burst and diffusion-controlled phases, being progesterone released faster at low pH. In addition, delivery extend in cows was affected mainly by particle size and hormone initial content, while the amount injected altered plasma concentration. Theoretical predictions with excellent accuracy were obtained. Conclusion: The mathematical model developed can help to find proper particle features to reach specific delivery rates in the animals. This not only save time, money and effort but also minimized experimentation with animals which is desired from an ethical point of view.