Taste Masking of Enalapril Maleate by the Precipitation Method.

BACKGROUND: Taste masking of bitter or unpleasant drugs is an important prerequisite to improve patient compliance, especially for children and elderly patients. We aimed at obtaining taste-masked microparticles intended for incorporation into orodispersible tablets (ODTs). We selected the precipitation method using enalapril maleate (ENA) as a model bitter-tasting drug and Eudragit EPO® as a pH sensitive polymer. AIM: The aim of this study was to obtain microparticles with enalapril maleate by the precipitation method in order to mask the bitter taste of the drug. MATERIALS AND METHODS: Nine models of enalapril maleate ­ Eudragit EPO® microparticles were prepared by the precipitation method at varied drug-polymer ratios. The models were characterized in terms of size, shape, production yield, drug content, encapsulation efficiency and moisture content. Fourier-transformed infrared spectroscopy, powder X-ray diffraction and differential scanning calorimetry were used to analyze possible interactions in the complex. In vitro drug release in simulated salivary fluid and in vivo taste evaluation in rats were realized to prove taste masking. RESULTS: The particle size distribution varied from 266.9 µm to 410.9 µm. The shape of the resulting particles was irregular. The production yield varied from 23.6% to 78.2%. The drug content ranged between 2.3% to 4.8%, encapsulation efficiency increased from 1.6% to 9.0%. In vitro drug release data indicated significant taste masking. CONCLUSION: Some of the obtained microparticles by the precipitation method showed satisfactory taste masking efficiency, which proved the taste masking feasibility of this method.

Optimization of Chitosan Microspheres Spray Drying via 32 Full Factorial Design.

BACKGROUND: Generally, the preparation of spray-dried microspheres is strongly affected by the process parameters. Particle size and production yield are mainly influenced by the spraying solution concentration and the pump rate of the spray dryer. AIM: The aim of this study was to assess optimum spray drying parameters - polymer concentration and pump rate required for the production of chitosan microspheres with high production yield and targeted for nasal administration particle size. MATERIALS AND METHODS: Full 32 factorial design was used to study the investigated parameters. Three different concentrations of the chitosan solution were selected: a low concentration of 1%, average concentration of 1.5% and high concentration of 2%. The rate of the peristaltic pump was also varied at three levels: low rate of 10%, medium rate of 14% and high rate of 18%. RESULTS: Nine models of chitosan microspheres were formulated and characterized in terms of shape, surface morphology, size, particle size distribution and production yield. The particles obtained from 2% chitosan solutions, sprayed at 10% pump rate were of the highest yield (64.33%) and appropriate for nasal administration median diameter (3,434 µm). CONCLUSION: The two investigated spray-drying parameters interact with each other and their influence on the production yield and the size of the chitosan microspheres should be evaluated together, instead of one at a time. The assessed process parameters allow the production of chitosan microparticles with high yield and desirable characteristics (size, size distribution and shape) for intranasal delivery.

Formulation and performance evaluation of betahistine dihydrochloride microspheres as sustained release systems.

UNLABELLED: Betahistine dihydrochloride is a histamine-like drug widely used in relieving the symptoms associated with Ménière's syndrome. Pharmacokinetic studies of betahistine have demonstrated that it has a short plasma half-life of 3-4 hours. In such cases frequent administration of the drug is required in order to keep plasma concentration within the therapeutic range. However, this may lead to noncompliance and aggravate patients' comfort. An advanced approach for achieving sustained release of drugs is their incorporation in microparticulate carriers. AIM: To design a sustained release microsphere formulation of betahistine providing reduced dose frequency and lower risk of side effects occurrence. MATERIALS AND METHODS: Betahistine-loaded chitosan microspheres were obtained via W/O emulsion solvent evaporation technique and were characterized for particle size, drug loading and entrapment efficiency. Drug release into phosphate buffer saline pH 7.4 was performed and dissolution profiles of the formulations were obtained. To study the mechanism of drug release from the microspheres the dissolution data was fitted to various mathematic models. RESULTS: Betahistine-loaded microspheres were produced with a high drug loading and entrapment efficiency. The microcarriers were spherical in shape with mean particle size of 3.82 µm to 7.69 µm. Betahistine release studies from the microspheres showed similar and slightly increasing dissolution profiles. The drug release proceeded in a controlled manner following Fickian diffusion. CONCLUSION: The obtained results suggest that betahistine-loaded chitosan microspheres prepared by solvent evaporation method are capable of sustained release of drugs and therefore can be used as drug delivery systems in the treatment of Ménière's syndrome.

Erucylphospho-N,N,N-trimethylpropylammonium (erufosine) is a potential antimyeloma drug devoid of myelotoxicity.

PURPOSE: Erufosine is an i.v. injectable alkylphosphocholine which is active against various haematological malignancies in vitro. In the present study, its effects on multiple myeloma (MM) cell lines and on murine and human hematopoietic progenitor cells (HPCs) were investigated. METHODS: The following MM cell lines were used: RPMI-8226, U-266 and OPM-2. The cytotoxicity of erufosine against these cell lines was determined by the MTT-dye reduction assay. Bcl-2, Bcl-X(L) and pAkt expression levels, activation of caspases, as well as cleavage of PARP, were studied by Western blotting. Migration was evaluated by a modified Boyden-chamber assay. The haematologic toxicity of erufosine was assessed using clonogenicity assays with normal HPCs of murine or human origin. RESULTS: Significant cytotoxic activity of erufosine against the MM cell lines was found. Comparison of the characteristics of erufosine-induced cell death in the three cell lines revealed a complex mode of action with apoptotic mechanisms prevailing in OPM-2 cells and non-apoptotic mechanisms prevailing in U-266 cells. The sensitivity of the MM cell lines to erufosine-induced apoptosis correlated inversely with the Bcl-X(L) expression level. Erufosine participated in synergistic interactions with various drugs. Furthermore, it showed potent migration-inhibiting activity in RPMI-8226 cells. Erufosine was not toxic to normal HPCs of murine or human origin and even stimulated progenitors from human umbilical cord blood to form granulocyte/macrophage colonies. Moreover, erufosine ameliorated the toxicity of bendamustine to murine HPCs. CONCLUSIONS: Overall, the data presented reveal that erufosine could have potential as an antimyeloma drug and deserves further development.