The aim of this study was the investigation of powder-based formulations for nasal administration... more The aim of this study was the investigation of powder-based formulations for nasal administration of tacrine hydrochloride. The anti-Alzheimer drug was encapsulated in mucoadhesive microparticles based on chitosan/pectin polyelectrolyte complexes. Microparticles were prepared by means of two different technological approaches (direct spray-drying and spray-drying followed by lyophilization) and analysed in terms of size, morphology and physico-chemical characteristics. Moreover, water uptake and mucoadhesion ability were evaluated as well as drug release and permeation behaviour. The results suggest that lyophilization favours the formation of small particle aggregates with a size of 10 μm, instead of single particles (size smaller than 5 μm) such as direct spray-drying. Particles obtained with the two loading methods present different functional properties according to the different physical state of the loaded drug and its possible interaction with chitosan/pectin complex. Moreover, the presence of different amount of chitosan and pectin in the complex influences their ability to hydrate, interact with mucin and favour drug permeation.
The aim of this work was to prepare vaginal inserts based on chitosan/carboxymethylcellulose poly... more The aim of this work was to prepare vaginal inserts based on chitosan/carboxymethylcellulose polyelectrolyte complexes for local delivery of chlorhexidine digluconate. Complexes were prepared with different chitosan/carboxymethylcellulose molar ratios at a pH value close to pK a interval of the polymers and were characterized in terms of physico-chemical properties, complexation yield and drug loading. Then complexes were used to prepare inserts as vaginal dosage forms and their physical handling, morphology, water-uptake ability and drug release properties as well as antimicrobial activity toward Candida albicans and Escherichia coli were evaluated. Results confirmed the ionic interaction between chitosan and carboxymethylcellulose and the influence of the charge amount on the complexation yield. Complexes were characterized by high values of drug loading and showed increasing water-uptake ability with the increase of carboxymethylcellulose amount. The selection of appropriate chitosan/ carboxymethylcellulose molar ratios allowed to obtain cone-like shaped solid inserts, easy to handle and able to hydrate releasing the drug over time. Finally, the formulated inserts showed antimicrobial activity against common pathogens responsible for vaginal infections.
Journal of Pharmaceutical and Biomedical Analysis, 2008
A fast and simple method based on LC with fluorescence detection has been developed for the deter... more A fast and simple method based on LC with fluorescence detection has been developed for the determination of insulin in innovative formulations consisting of microparticles and inserts for oral and nasal drug administration, respectively. A reverse-phase C8 column and a mobile phase composed of pH 3.7, 40 mM sodium sulphate solution and acetonitrile (24%, v/v) were employed. Using isocratic elution at 1.0 mL/min flow, analysis is completed within 7 min. Three different kinds of spray-dried microparticles were analysed, consisting of an insulin loaded core composed of chitosan salts (chitosan succinate, chitosan adipate or chitosan suberate) coated with stearic acid. Nasal inserts consisted of chitosan/hyaluronate polyelectrolyte complexes which were loaded with insulin and freeze-dried. Insulin was extracted from both the oral and nasal formulations using pH 7.4 phosphate buffer. The employment of fluorescence detection (lambda(exc) = 276 nm, lambda(em) = 306 nm) granted high selectivity, with no interference from the matrix. Full method validation was performed with good results in terms of linearity (insulin concentration range 0.10-30.0 microg/mL), LOD (0.03 microg/mL) and LOQ (0.10 microg/mL), precision (R.S.D.%<3.6) and accuracy (recovery percentage>90.0%). Insulin content in innovative formulations, expressed as percentage w/w, resulted to be between 0.90 and 0.97 for oral innovative formulations, while an average value of 342 microg of insulin was found in a single nasal insert, in good agreement with preparative protocols.
The objective of this study was the development of chitosan/hyaluronan transdermal films to impro... more The objective of this study was the development of chitosan/hyaluronan transdermal films to improve bioavailability of thiocolchicoside. This approach offers the possibility to elude the first-pass metabolism and at the same time it is able to provide a predictable and extended duration of activity. Films were prepared by casting and drying of aqueous solutions containing different weight ratios of chitosan and hyaluronan and characterized for their physico-chemical and functional properties. In accordance with polymeric composition of films and, therefore, with the amount of the net charge after the complexation, films containing the same weight ratio of chitosan and hyaluronan showed lower water uptake ability with respect to films containing only one polymeric species or an excess of chitosan or hyaluronan. Moreover, the lower the hydration of the polymeric network, the lower is the drug diffusion through the films and its permeation through the skin. This study clearly confirmed that the selection of a suitable polymeric weight ratio and appropriate preparative conditions allows the modulation of film functional properties, suggesting that these formulations could be used as a novel technological platform for transdermal drug delivery.
The aim of this study was the investigation of powder-based formulations for nasal administration... more The aim of this study was the investigation of powder-based formulations for nasal administration of tacrine hydrochloride. The anti-Alzheimer drug was encapsulated in mucoadhesive microparticles based on chitosan/pectin polyelectrolyte complexes. Microparticles were prepared by means of two different technological approaches (direct spray-drying and spray-drying followed by lyophilization) and analysed in terms of size, morphology and physico-chemical characteristics. Moreover, water uptake and mucoadhesion ability were evaluated as well as drug release and permeation behaviour. The results suggest that lyophilization favours the formation of small particle aggregates with a size of 10 μm, instead of single particles (size smaller than 5 μm) such as direct spray-drying. Particles obtained with the two loading methods present different functional properties according to the different physical state of the loaded drug and its possible interaction with chitosan/pectin complex. Moreover, the presence of different amount of chitosan and pectin in the complex influences their ability to hydrate, interact with mucin and favour drug permeation.
The aim of this work was to prepare vaginal inserts based on chitosan/carboxymethylcellulose poly... more The aim of this work was to prepare vaginal inserts based on chitosan/carboxymethylcellulose polyelectrolyte complexes for local delivery of chlorhexidine digluconate. Complexes were prepared with different chitosan/carboxymethylcellulose molar ratios at a pH value close to pK a interval of the polymers and were characterized in terms of physico-chemical properties, complexation yield and drug loading. Then complexes were used to prepare inserts as vaginal dosage forms and their physical handling, morphology, water-uptake ability and drug release properties as well as antimicrobial activity toward Candida albicans and Escherichia coli were evaluated. Results confirmed the ionic interaction between chitosan and carboxymethylcellulose and the influence of the charge amount on the complexation yield. Complexes were characterized by high values of drug loading and showed increasing water-uptake ability with the increase of carboxymethylcellulose amount. The selection of appropriate chitosan/ carboxymethylcellulose molar ratios allowed to obtain cone-like shaped solid inserts, easy to handle and able to hydrate releasing the drug over time. Finally, the formulated inserts showed antimicrobial activity against common pathogens responsible for vaginal infections.
Journal of Pharmaceutical and Biomedical Analysis, 2008
A fast and simple method based on LC with fluorescence detection has been developed for the deter... more A fast and simple method based on LC with fluorescence detection has been developed for the determination of insulin in innovative formulations consisting of microparticles and inserts for oral and nasal drug administration, respectively. A reverse-phase C8 column and a mobile phase composed of pH 3.7, 40 mM sodium sulphate solution and acetonitrile (24%, v/v) were employed. Using isocratic elution at 1.0 mL/min flow, analysis is completed within 7 min. Three different kinds of spray-dried microparticles were analysed, consisting of an insulin loaded core composed of chitosan salts (chitosan succinate, chitosan adipate or chitosan suberate) coated with stearic acid. Nasal inserts consisted of chitosan/hyaluronate polyelectrolyte complexes which were loaded with insulin and freeze-dried. Insulin was extracted from both the oral and nasal formulations using pH 7.4 phosphate buffer. The employment of fluorescence detection (lambda(exc) = 276 nm, lambda(em) = 306 nm) granted high selectivity, with no interference from the matrix. Full method validation was performed with good results in terms of linearity (insulin concentration range 0.10-30.0 microg/mL), LOD (0.03 microg/mL) and LOQ (0.10 microg/mL), precision (R.S.D.%<3.6) and accuracy (recovery percentage>90.0%). Insulin content in innovative formulations, expressed as percentage w/w, resulted to be between 0.90 and 0.97 for oral innovative formulations, while an average value of 342 microg of insulin was found in a single nasal insert, in good agreement with preparative protocols.
The objective of this study was the development of chitosan/hyaluronan transdermal films to impro... more The objective of this study was the development of chitosan/hyaluronan transdermal films to improve bioavailability of thiocolchicoside. This approach offers the possibility to elude the first-pass metabolism and at the same time it is able to provide a predictable and extended duration of activity. Films were prepared by casting and drying of aqueous solutions containing different weight ratios of chitosan and hyaluronan and characterized for their physico-chemical and functional properties. In accordance with polymeric composition of films and, therefore, with the amount of the net charge after the complexation, films containing the same weight ratio of chitosan and hyaluronan showed lower water uptake ability with respect to films containing only one polymeric species or an excess of chitosan or hyaluronan. Moreover, the lower the hydration of the polymeric network, the lower is the drug diffusion through the films and its permeation through the skin. This study clearly confirmed that the selection of a suitable polymeric weight ratio and appropriate preparative conditions allows the modulation of film functional properties, suggesting that these formulations could be used as a novel technological platform for transdermal drug delivery.
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