An innovative carrier for the formulation of amorphous solid dispersion by hot-melt extrusion with no further downstream processes: a case study with indomethacin.

The aim of this work was to study the possibility to use SepitrapTM as a carrier for the formulation of amorphous solid dispersions by HME (hot melt extrusion) processing aiming solubility enhancement of poorly water-soluble drugs. SepitrapTM is a microencapsulated powder solubilizer designed to simplify the manufacture of drugs in oral solid forms, not yet tested for this purpose. The performance of SepitrapTM was evaluated in HME processing for amorphous solid dispersions of poorly-water soluble drugs with indomethacin as a model drug. The study was conducted using a twin-screw extruder, two compositions of SepitrapTM and different loads of indomethacin, demonstrating that SepitrapTM could represent a new range of carriers for amorphous solid dispersions for HME processing, reducing necessary downstream steps such as grinding.

Solid amorphous formulations for enhancing solubility and inhibiting Erlotinib crystallization during gastric-to-intestinal transfer.

The objective of this study was to improve the solubility and inhibit the crystallisation during the gastric-to-intestinal transfer of Erlotinib (ERL), a small molecule kinase inhibitor (smKI) compound class, which is classified as class II drug in the Biopharmaceutical Classification System (BCS). A screening approach combining different parameters (solubility in aqueous media, inhibitory effect of drug crystallisation from supersaturated drug solutions) was applied to selected polymers for the development of solid amorphous dispersions of ERL. ERL solid amorphous dispersions formulations were then prepared with 3 different polymers (Soluplus®, HPMC-AS-L, HPMC-AS-H) at a fixed drug: polymer ratio (1:4) by two different production methods (spray drying and hot melt extrusion). The spray-dried particles and cryo-milled extrudates were characterized by thermal properties, shape and particle size, solubility and dissolution behavior in aqueous media. The influence of the manufacturing process on these solid characteristics was also identified during this study. Based on the obtained results, it is concluded that the cryo-milled extrudates of HPMC-AS-L displayed better performance (enhanced solubility, reduced ERL crystallization during the simulated gastric-to-intestinal transfer) and represents a promising amorphous solid dispersion formulation for oral administration of ERL.

Determination of drug-polymer solubility from supersaturated spray-dried amorphous solid dispersions: A case study with Efavirenz and Soluplus®.

Amorphous solid dispersions (ASDs) are found to be a well-established strategy for overcoming limited aqueous solubility and poor oral bioavailability of active pharmaceutical ingredients (APIs). One of the main parameters affecting ASDs physical stability is the API solubility in the carrier, because this value determines the maximal API load without a risk of phase separation and recrystallization. Phase-diagrams can be experimentally obtained by following the recrystallization of the API from a supersaturated homogeneous API-polymer solid solution, commonly produced by processes as solvent casting or comilling, which are very time-consuming (hours). The work deals with the construction of a temperature-composition EFV-Soluplus® phase diagram, from a thermal study of recrystallization of a supersaturated solid solution (85 wt% in EFV) generated by spray drying. This supersaturated solution is kept at a given annealing temperature to reach the equilibrium state and the amount that still remains dispersed in the polymer carrier at this equilibrium temperature is determined by means of the new glass transition temperature of the binary mixture. From our knowledge, this is the first study employing a fast process (spray drying) to prepare a supersaturated solid solution of an API in a polymer aiming to determine a temperature-composition phase diagram. The EFV solubility in Soluplus ranges from 20 wt% at 25 °C to 30 wt% at 40 °C. It can be a very useful preformulation tool for researchers studying amorphous solid dispersions of Efavirenz in Soluplus, to assist for predicting the stability of EFV-Soluplus ASDs at different EFV loadings and under different thermal conditions.

Biocompatible magnetic microspheres for Use in PDT and hyperthermia.

Loaded microspheres with a silicon (IV) phthalocyanine derivative (NzPC) acting as a photosensitizer were prepared from polyhydroxybutyrate-co-valerate (PHBHV) and poly(ecaprolactone) (PCL) polymers using the emulsification solvent evaporation method (EE). The aim of our study was to prepare two systems of these biodegradable PHBHV/PCL microspheres. The first one containing only photosensitizer previously incorporated in the PHBHV and poly(ecaprolactone) (PCL) microspheres and the second one with the post magnetization of the DDS with magnetic nanoparticles. Magnetic fluid is successfully used for controlled incorporation of nanosized magnetic particles within the micron-sized template. This is the first time that we could get a successful pos incorporation of nanosized magnetic particles in a previously-prepared polymeric template. This procedure opens a great number of possibilities of post-functionalization of polymeric micro or nanoparticles with different bioactive materials. The NzPC release profile of the systems is ideal for PDT, the zeta potential and the size particle are stable upon aging in time. In vitro studies were evaluated using gingival fibroblastic cell line. The dark citotoxicity, the phototoxicity and the AC magnetic field assays of the as-prepared nanomagnetic composite were evaluated and the cellular viability analyzed by the classical test of MTT.

Preparation and characterization of carnauba wax nanostructured lipid carriers containing benzophenone-3.

Nanostructured lipid carriers (NLCs) are potential active delivery systems based on mixtures of solid lipids and liquid oil. In this paper, aqueous dispersions of NLCs were prepared by a hot high-pressure homogenization technique using carnauba wax as the solid lipid and isodecyl oleate as the liquid oil. The preparation and stability parameters of benzophenone-3-loaded NLCs have been investigated concerning particle size, zeta potential and loading capacity to encapsulate benzophenone-3, a molecular sunscreen. The current investigation illustrates the effect of the composition of the lipid mixture on the entrapment efficiency, in vitro release and stability of benzophenone-3-loaded in these NLCs. A loading capacity of approximately 5% of benzophenone-3 (m(BZ-3) /m(lipids) ) was characteristic of these systems.

Assessing workshops on sexuality with Argentinian youth.

PIP: Workshops on sexuality for working-class Argentinean boys and girls 11-22 years of age, sponsored by the Foundation for Studies and Research on Women, have provided young people with a supportive environment for the exploration of reproductive health issues. The workshops have been held in schools, clubs, institutions for minors, health facilities, and community centers and complemented by workshops for parents, teachers, and other adults. Pre- and post-workshop questionnaires are administered to assess knowledge gains. Use of a gender-sensitive male coordinator has increased the participation of adolescent males and provided them with a role model. However, gender-related issues are better accepted by participants when introduced by peer educators rather than adults. At the conclusion of the workshops, young people produce songs, posters, drawings, and poems that reflect the educational content and are displayed in their communities. Although girls are preoccupied with a fear of pregnancy, both boys and girls do not perceive themselves as at risk of human immunodeficiency virus. Adolescents in rural areas are more sexually active than their urban counterparts. Finally, adolescent females report difficulties negotiating safe sex due to fears of being abandoned by their boyfriends.^ieng