Thermosensitive in situ nanocomposite of rivastigmine hydrogen tartrate as an intranasal delivery system: Development, characterization, ex vivo permeation and cellular studies.

Intranasal administration of pharmaceutical compounds is gaining considerable attention as an alternative route for localized/systemic drug delivery. However, insufficient therapeutic efficacy of drugs via this route seems to be a major challenge for development of de novo intranasal formulations. This shortcoming can be overcome by simultaneous utilization of a nanoparticulate delivery system with a polymeric gel network. Therefore, the main aim of the present study was to develop erodible in-situ gel forming systems of poloxamer 407® (P407) as a promising platform, capable of prolonging rivastigmine hydrogen tartrate (RHT) release from the embedded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). PLGA NPs containing RHT were formulated and characterized, then were embedded in P407 gel forming matrix and analyzed in terms of viscosity, stability, gelation temperature, loading efficiency and mucoahesive behavior. The cytotoxicity of NPs was evaluated on A549 cell line using MTT assay. Cellular uptake of the NPs was also measured by means of fluorescence microcopy and flow cytometry analyses. The formulations were finally evaluated for their permeability across sheep nasal mucosa. A linear dependence of sol-gel temperature (Tsol-gel) on the P407 concentration was observed, and a P407 content of 18% was selected. The loading efficiencies of formulations were found to be around 100.22-104.31%. The RHT-loaded NPs showed a suitable cytocompatibility on A549 cells with a time-dependent increase in cellular uptake. Besides, nanocomposites showed higher amounts of drug permeation through nasal sheep mucosa than plain drug gel. Taken all, it is concluded that the formulated nanocomposites may be considered as useful drug delivery systems for the nasal delivery of RHT with enhanced therapeutic efficacy.

Study of antimicrobial effects of vancomycin loaded PLGA nanoparticles against enterococcus clinical isolates.

Researchers have demonstrated that antimicrobial agents in nanoparticle (NP) forms have better activities. Vancomycin (VCM), as a glycopeptide antibiotic with antimicrobial activity against gram positive bacteria, is poorly absorbed from the intestinal tract. Enterococcus is a genus of bacteria that became resistant to a wide range of antibiotics in last decades, and cause severe infections in hospitalized patients. This paper describes preparation of VCM--loaded poly (lactic-co-glycolic acid) (PLGA) NPs and compares the antimicrobial effects with drug solution against clinical Enterococcus isolates. VCM-loaded PLGA NPs were fabricated by W1/O/W2 solvent evaporation method. The comparison of obtained Minimum Inhibitory Concentration (MIC) values showed a significant decrease in the antimicrobial effect of VCM -loaded NPs. Results also indicated that the potency of the NPs against VCM resistant isolates of Enterococcus was less than VCM susceptible isolates. The reduced antimicrobial effect of formulated NPs in invitro condition is perhaps related to the strong electrostatic linkage between hydrophilic drug (VCM) and hydrophobic polymer (PLGA) that lead to the slow release of the antibiotic from polymeric NPs.

Effect of formulation and processing variables on the characteristics of tolmetin microspheres prepared by double emulsion solvent diffusion method.

The aim of this study was to evaluate microencapsulated controlled release preparations of tolmetin sodium using ethylcellulose as a retardant material. Microspheres were prepared by using water-in-oil-in-oil (W/O(1)/O(2)) double-emulsion solvent diffusion method, using different ratios of ethylcellulose to tolmetin sodium. Span 80 was used as the droplet stabilizer and n-hexane was added to harden the microspheres. The prepared microspheres were characterized for their micromeritic properties, drug content, loading efficiency, production yield, and particle size. Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray powder diffractometry and scanning electron microscopy were used to characterize microparticles. The in vitro release studies were performed in pH 1.2 and 7.4. The prepared microspheres were spherical in shape. The drug-loaded microspheres showed near to the theoretical of entrapment and release was extended up to 24. The X-ray diffractogram and differential scanning thermographs showed amorphous state of the drug in the microspheres. It was shown that the drug: polymer ratio, stirring rate, volume of dispersing medium and surfactant influenced the drug loading, particle size and drug release behavior of the formed microparticles. The results showed that, generally, an increase in the ratio of drug: polymer (0.5:1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. The in vitro release profile could be modified by changing various processing and formulation parameters to give a controlled release of drug from the microparticules. The release of tolmetin was influenced by the drug to polymer ratio and particle size and was found to be diffusion and erosion controlled. The best-fit release kinetic was achieved with Peppas model.

Physico-mechanical and dissolution behaviours of ibuprofen crystals crystallized in the presence of various additives.

BACKGROUND AND THE PURPOSE OF THE STUDY: The success of any direct-tableting procedure is strongly affected by the quality of the crystals used in the process. Ibuprofen is a poorly compactible drug with a high tendency for capping. In order to use ibuprofen in direct compression formulations, physico-mechanical properties of ibuprofen should be improved considerably. The aim of the present investigation was to employ crystallization techniques in order to improve the physico- mechanical properties of ibuprofen for direct compression. METHODS: The experimental methods involved the preparation of ibuprofen crystals by solvent change technique. Ibuprofen was dissolved in ethanol and crystallized out with water in the absence or presence of various hydrophilic additives (PEG 6000, 8000, Brij 98P and polyvinyl alcohol 22000, PVA (22000)) with different concentrations. The physico-mechanical properties of the ibuprofen crystals were studied in terms of flow, density, tensile strength and dissolution behaviour. Morphology of ibuprofen crystals was studied by scanning electron microscopic (SEM). Solid state of the recrystallized particles was also investigated using differential scanning calorimeter (DSC) and FT-IR. RESULTS: Ibuprofen samples crystallized in the presence of PEG 6000 and 8000 and PVA showed remarkable increase in the tensile strengths of the directly compressed tablets, while some other additives, i.e. Brij 98P did not produce improved ibuprofen crystals. Ibuprofen powders made from particles obtained in the presence of PVA and Brij 98P showed similar dissolution profiles to the commercial ibuprofen particles. DSC and FT-IR results ruled out any significant interaction between ibuprofen and additives except for the samples crystallized in the presence of PEG 8000. CONCLUSION: The crystal habit of ibuprofen can be altered successfully by the crystallization technique which was developed in this study. The crystals developed in the presence of certain additives can be recommended for direct compression.

Development of theophylline floating microballoons using cellulose acetate butyrate and/or Eudragit RL 100 polymers with different permeability characteristics.

The objective of the present investigation was to design a sustained release floating microcapsules of theophylline using two polymers of different permeability characteristics; Eudragit RL 100 (Eu RL) and cellulose acetate butyrate (CAB) using the oil-in-oil emulsion solvent evaporation method. Polymers were used separately and in combination to prepare different microcapsules. The effect of drug-polymer interaction was studied for each of the polymers and for their combination. Encapsulation efficiency, the yield, particle size, floating capability, morphology of microspheres, powder X-ray diffraction analysis (XRD), and differential scanning calorimetry (DSC) were evaluated. The in vitro release studies were performed in PH 1.2 and 7.4. The optimized drug to polymer ratios was found to be 4:1 (F(2)) and 0.75:1 (F'(2)) with Eu RL and CAB, respectively. The best drug to polymer ratio in mix formulation was 4:1:1 (theophylline: Eu RL: CAB ratio). Production yield, loading efficiencies, and particle size of F(2) and F'(2) were found to be 59.14% and 45.39%, 73.93% and 95.87%, 372 and 273 micron, respectively. Microsphere prepared with CAB showed the best floating ability (80.3 ± 4.02% buoyancy) in 0.1 M HCl for over 12 h. The XRD and DSC showed that theophylline in the drug loaded microspheres was stable and in crystaline form. Microparticles prepared using blend of Eu RL and CAB polymers indicated more sustained pattern than the commercial tablet (P<0.05). Drug loaded floating microballoons prepared of combination of Eu RL and CAB with 1:1 ratio were found to be a suitable delivery system for sustained release delivery of theophylline which contained lower amount of polymer contents in the microspheres.

The microsponge delivery system of benzoyl peroxide: preparation, characterization and release studies.

Benzoyl peroxide (BPO) is commonly used in topical formulations for the treatment of acne and athletes foot. Skin irritation is a common side effect, and it has been shown that controlled release of BPO from a delivery system to the skin could reduce the side effect while reducing percutaneous absorption. Therefore, the aim of the present study was to produce ethylcellulose microparticles containing BPO which were able to control the release of BPO to the skin. In order to optimize the microparticle formulation, factors affecting the physical properties of microparticles were also investigated. Benzoyl peroxide microparticles were prepared using an emulsion solvent diffusion method by adding an organic internal phase containing benzoyl peroxide, ethyl cellulose and dichloromethane into a stirred aqueous phase containing polyvinyl alcohol. Drug content, particle size analysis and loading yield were determined in the prepared microparticles. BPO microparticles were then incorporated into standard vehicles for release studies. Scanning electron microscopy was used to study the shape and morphology of the microsponges. The micrograph of microsponges showed that they were spherical in shape and contained pores. These pores resulted from the diffusion of solvent from the surface of the microparticles and thus the particles were designated as microsponges. It was shown that the drug:polymer ratio, stirring rate, volume of dispersed phase influenced the particle size and drug release behavior of the formed microsponges and that the presence of emulsifier was essential for microsponge formation. The results showed that, generally, an increase in the ratio of drug:polymer resulted in a reduction in the release rate of BPO from microsponges which was attributed to a decreased internal porosity of the microsponges.