Solid lipid nanoparticles with and without hydroxypropyl-ß-cyclodextrin: a comparative study of nanoparticles designed for colonic drug delivery.

New solid lipid nanoparticles (SLN), composed of Compritol ATO888 (C) and hydroxypropyl-ß-cyclodextrin (HP), were developed in order to study a new colon-specific formulation for diclofenac sodium (D) delivery. The prepared batches differ from each other by the molecular ratio between HP and D and by the composition of the matrix. Nanoparticles composed of an exclusively lipid matrix and nanoparticles with an oligomeric and lipid matrix were compared in order to establish the effect of both components on the drug delivery tests performed. The SLN preparation method was based on the oil/water hot homogenization process. Emulsions produced were cooled at room temperature and lyophilized in order to obtain dried nanoparticles; possible damage to nanoparticle shape and size was avoided by the addition of cryoprotectants to the aqueous dispersion of nanoparticles before exsiccation. An in vitro toxicity study was performed using CaCo(2) cells to establish the safety of the prepared SLN. Data obtained showed that production method studied guarantees emulsions composed of nanosized drops which can be dried by lyophilization into SLN with a size range of 300-600 nm. In vitro and ex vivo tests demonstrated that dried SLN can be considered as colon delivery systems; however, the matrix composition as well as the presence of cryoprotectant on their surface influences the release and permeation rate of D. The in vitro toxicity studies indicated that the SLN are well tolerated.

Ketoprofen spray-dried microspheres based on Eudragit RS and RL: study of the manufacturing parameters.

The preparation of ketoprofen spray-dried microspheres can be affected by the long drug recrystallization time. Polymer type and drug-polymer ratio as well as manufacturing parameters affect the preparation. The purpose of this work was to evaluate the possibility to obtain ketoprofen spray-dried microspheres using the Eudragit RS and RL; the influence of the spray-drying parameters on morphology, dimension, and physical stability of microspheres was studied. Ketoprofen microspheres based on Eudragit blend can be prepared by spray-drying and the nebulization parameters do not influence significantly particle properties; nevertheless, they can be affected by drying and storage methods. No effect of the container material is found.

Bio-based topical system for enhanced salicylic acid delivery: preparation and performance of gels.

OBJECTIVES: New salicylic acid (SA)-loaded gels were developed using excipients made from renewable materials, and our goal was to improve drug permeation in the topical treatment of acne vulgaris. METHODS: We studied the preparation parameters to obtain suitable gel formulations. Only naturally occurring polymers were used as gelling agents. Two hydrogels and three lipogels were selected and characterized in terms of drug loading, pH, viability cells, rheology, mechanical properties and in vitro permeation; these hydrogels and lipogels were compared with the traditional ointment. We also evaluated skin parameters before and after gel application. KEY FINDINGS: The formulations that we studied are non-Newtonian fluids; they have high drug loading and suitable mechanical properties. Lipogels exhibit a slower and more linear in vitro permeation profile compared with hydrogels. The different vehicles that we used affected drug permeation and improve patient compliance. Cytotoxicity studies suggest that all of the formulations are non-toxic. CONCLUSIONS: Lipogels demonstrate appropriate technological features and improved performance compared with the traditional ointment with regard to their composition. Lipogels may represent a new bio-based topical system for SA delivery. The use of 'green' excipients leads to 'skin-friendly' formulations that are able to satisfy environmental safety.

Evaluation of the effect of hydroxypropyl-ß-cyclodextrin on topical administration of milk thistle extract.

Two water in oil emulsions composed by eudermic ingredients as glycerin, cocoa butter, almond oil and a variety of lipids, were enriched respectively with milk thistle dry extract (MT) or with a binary complex composed by MT and hydroxypropyl-ß-cyclodextrin (HP) (1:4 w/w) correspondent to 1% (w/w) in sylimarine in order to obtain two different emulsions designed for the skin delivery and determine influence of hydroxypropyl-ß-cyclodextrin on the extract delivery and permeation. Uv-vis spectrophotometric analyses demonstrated that phytocomplex formation influences the finding of MT after the complexation process and the in vitro antioxidant activity. Further in vitro and ex vivo experiments demonstrated that the penetration capability of MT from formulations is strictly influenced by the phytocomplex able to control MT permeation; moreover phytocomplex increases flavonoids stability during the in vitro tests. Additionally, in vivo studies showed that the penetration into the stratum corneum of the active ingredients is effectively achieved by the phytocomplex formation, in fact about 80% of MT is absorbed by the skin along 1h despite the 30% of MT not complexed absorbed during the same period.

Development of solid nanoparticles based on hydroxypropyl-ß-cyclodextrin aimed for the colonic transmucosal delivery of diclofenac sodium.

OBJECTIVES: Nanoparticles were designed for the oral administration and transmucosal colon delivery of drugs. METHODS: Preparation parameters were studied in order to develop solid pH-dependent drug-release nanoparticles, constituted by hydroxypropyl-ß-cyclodextrin and/or Eudragit(®) L100 loaded with diclofenac sodium. Nanoemulsions were prepared by the emulsion-evaporation method using various homogenizers. Different preparative conditions were tested. The emulsions obtained were analysed in terms of size and then dried to obtain solid nanoparticles which were characterized in vitro (particle size, morphology, dissolution, solid state characterization). The effect of nanoparticles on drug permeation through synthetic membranes, colonic pig mucosa and Caco2 cell line were performed. Toxicity studies were carried out to assess the safety of the raw materials used and the nanosystems produced. KEY FINDINGS: Appropriate parameters to obtain nanoemulsions stable enough to be desiccated were determined: Panda NS100L was the most suitable homogenizer for the preparation; particle size ranged between 100 and 600 nm depending on the production method. Solid nanoparticles were obtained by an exsiccation process, which does not modify the mean size. pH-dependent drug-release nanoparticles were obtained. The nanoencapsulation process decreased the crystallinity of the drug. Materials and nanoparticles were highly biocompatible. Transmucosal delivery of drug is dependent on the polymer and the test employed: cyclodextrin improved drug permeation across colonic pig mucosa. CONCLUSIONS: Formulations containing hydroxypropyl-ß-cyclodextrin represent new colon-targeted nanoparticles for transmucosal delivery of drugs.