Rheological temperature sweeping in a quality by design approach for formulation development and optimization.

Many topical drug products are multi-phase systems which are prone to phase separation exhibiting a high risk for not meeting the critical quality attributes (CQAs) of a pharmaceutical product such as uniform active pharmaceutical ingredient (API) distribution and physical homogeneity. In order to investigate and control these CQAs a rheological temperature sweeping (RTS) method was implemented and refined to enable quantification of these characteristics within a quality by design (QbD) approach. For method implementation, emulsion and ointment compositions were prepared within a design of experiments (DoE) and critical responses from RTS were extracted via principal component analysis (PCA) in a multivariate data analysis (MVA) approach.

Design of lipid microparticle dispersions based on the physicochemical properties of the lipid and aqueous phase.

Lipid microparticle (LMP) dispersions may be utilized as novel pharmaceutical dosage forms for different administration routes. The particle size and particle size distribution of the LMPs can be classified to the most crucial specifications for therapeutical and research applications. The size parameters can be adjusted via the physicochemical properties of the inner lipid and the outer aqueous phase.

Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route.

Lipid nanoparticles (LN) such as solid lipid nanoparticles (SLN) and nanolipid carriers (NLC) feature several claimed benefits for topical drug therapy including biocompatible ingredients, drug release modification, adhesion to the skin, and film formation with subsequent hydration of the superficial skin layers. However, penetration and permeation into and across deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). As different kinds of nanoparticles provide the potential for penetration into hair follicles (HF) LN are applicable drug delivery systems (DDS) for this route in order to enhance the dermal and transdermal bioavailability of active pharmaceutical ingredients (API).

Comparison of rheological properties, follicular penetration, drug release, and permeation behavior of a novel topical drug delivery system and a conventional cream.

A novel adapalene-loaded solid lipid microparticle (SLMA) dispersion as a topical drug delivery system (TDDS) for follicular penetration has been introduced. The objective of the present study was to investigate the rheological properties, the follicular penetration with differential tape stripping on porcine ear skin, the drug release in sebum and stratum corneum (SC) lipid mixtures, and the permeation behavior across human SC in comparison with a commercially available cream as standard. Physicochemical characterization reveals that adapalene is homogeneously distributed within the SLMA dispersion and chemically stable for at least 24 weeks.

Development, formulation, and characterization of an adapalene-loaded solid lipid microparticle dispersion for follicular penetration.

The model retinoid adapalene was formulated in a novel solid lipid microparticle (SLM) dispersion as a topical drug delivery system for transport of the active pharmaceutical ingredient (API) into hair follicle orifices. The aims of the investigations were the solid-state characterization of the lipid matrix (LM) with wide angle X-ray diffraction (WAXD) and hot-stage light microscopy (HS), the design space analysis of the developed SLM dispersion with a Box-Behnken design, the stability study of the manufactured formulation for particle size with laser diffraction and polarization intensity differential scattering (LD/PIDS) and thermal behavior with differential scanning calorimetry (DSC), and the structure analysis of the SLM dispersion with light microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The formulation showed a constant mean particle size (MPS) of 4.

Facilitation of spinal NMDA receptor currents by spillover of synaptically released glycine.

In the mammalian CNS, N-methyl-D-aspartate (NMDA) receptors serve prominent roles in many physiological and pathophysiological processes including pain transmission. For full activation, NMDA receptors require the binding of glycine. It is not known whether the brain uses changes in extracellular glycine to modulate synaptic NMDA responses.