The notion of controlled release has been known since the 1930s, but was not significantly develo... more The notion of controlled release has been known since the 1930s, but was not significantly developed until the 1970s. At that time, Alza introduced the concept of a "therapeutic system" and proposed new pharmaceutic formulations. Over time, the idea became one of controlled drug delivery and today concerns not only one rate of release but also the site of release of the active substance. We present here definitions, fundamentals and advantages and disadvantages of currently marketed systems and provide examples illustrating oral, transdermal and respiratory delivery systems. Current research is also examined.
A simple and sensitive HPLC method for the quantification of budesonide in skin layers was develo... more A simple and sensitive HPLC method for the quantification of budesonide in skin layers was developed and validated. Budesonide was extracted from stratum corneum, epidermis and dermis by means of a mixture of acetonitrile:water (recovery > 90%). Budesonide quantification was performed with a RP-C18 column using methanol and water mixture (69:31, v/v) as mobile phase, pumped at 0.8 ml/min. The absorbance was monitored at 254 nm. The method resulted to be selective, linear in the range 0.05-5 or 10 μg/ml, precise and accurate. LLOQ resulted to be 0.05 μg/ml. The developed method appeared to be appropriate for the quantification of budesonide in skin layers at the end of in vitro permeation experiments since the recovery of the applied dose was 97 ± 1%, in line with requirement of the OECD guideline for the testing of the chemicals (Skin absorption: in vitro method).
Estradiol transdermal application still represents a relevant topic due to the recent controversi... more Estradiol transdermal application still represents a relevant topic due to the recent controversies about hormone replacement therapy, its increasing potential in the treatment of skin aging and wound healing, and the new use of its derivatives in the transdermal contraceptive treatment. The aim of our work was to verify if fresh or frozen rabbit ear skin can be a suitable skin model to study in vitro estradiol transdermal absorption. Fresh rabbit ear skin demonstrated a reasonable model of human epidermis in the investigation of estradiol permeation starting from both solutions and commercial patches.
International Journal of Pharmaceutics, Feb 1, 2001
Triptorelin is a decapeptide analog of luteinizing hormone releasing hormone, currently used for ... more Triptorelin is a decapeptide analog of luteinizing hormone releasing hormone, currently used for the treatment of sex-hormones dependents diseases. The aim of this work was to prepare triptorelin-loaded nanospheres useful for transdermal iontophoretic administration. Nanospheres were prepared with the double emulsion/solvent evaporation technique. The effect of three parameters on the encapsulation efficiency has been determined: the role of the pH of the internal and external aqueous phases, the nature of the organic solvent and the effect of three different poly(lactide-co-glycolide) (PLGA) co-polymers. Particle size, zeta potential and release kinetics were also determined. The encapsulation efficiency varied from 4 to 83% reaching the maximum value when both the internal and the external water phases were brought to pH 7 (isoelectric point of the peptide), methylene chloride was used as solvent of the copolymers and PLGA rich in free carboxylic groups was employed. The release profiles obtained with this co-polymer were characterized by the absence of burst effect. This behavior as well as the high encapsulation efficiency was explained by an ionic interaction occurring between the peptide and the co-polymer. This supports the already expressed theory that the release of peptides and proteins from PLGA nanospheres is also governed by the affinity of the encapsulated molecule versus the polymer. The obtained nanoparticles, regarding their size, amount encapsulated and zeta potential, were shown to be suitable for transdermal iontophoretic administration.
Non-invasive drug delivery to the posterior segment of the eye represents an important unmet medi... more Non-invasive drug delivery to the posterior segment of the eye represents an important unmet medical need, and trans-scleral delivery could be an interesting solution. This review analyses the possibility of trans-scleral drug delivery for high molecular weight compounds, such as proteins and genetic material, which currently represent the most innovative and efficacious molecules for the treatment of many diseases of the posterior segment of the eye. The paper reviews all the barriers, both static and dynamic, involved in trans-scleral administration of drugs, trying to elucidate the role of each of them in the specific case of macromolecules. Delivery systems to sustain drug release and enhancing strategies to improve trans-scleral penetration are also described. Finally, the review approaches the use of computational models as a screening tool to evaluate the feasibility of trans-scleral administration for macromolecules.
Corticosteroids, although highly effective for the treatment of both anterior and posterior ocula... more Corticosteroids, although highly effective for the treatment of both anterior and posterior ocular segment inflammation, still nowadays struggle for effective drug delivery due to their poor solubilization capabilities in water. This research work aims to develop nanostructured lipid carriers (NLC) intended for periocular administration of dexamethasone acetate to the posterior segment of the eye. Pre-formulation studies were initially performed to find solid and liquid lipid mixtures for dexamethasone acetate solubilization. Pseudoternary diagrams at 65 °C were constructed to select the best surfactant based on the macroscopic transparency and microscopic isotropy of the systems. The resulting NLC, obtained following an organic solvent-free methodology, was composed of triacetin, Imwitor® 491 (glycerol monostearate >90%) and tyloxapol with Z-average = 106.9 ± 1.2 nm, PDI = 0.104 ± 0.019 and zeta potential = −6.51 ± 0.575 mV. Ex vivo porcine sclera and choroid permeation studies ...
This work aims at investigating the nicotinamide (NA)-ethyl-paraben (EP) binary system both in so... more This work aims at investigating the nicotinamide (NA)-ethyl-paraben (EP) binary system both in solution and in the solid state. In particular, the apparent EP solubility in water was studied in the presence of different NA concentrations (between 0.28 and 1.64 M). It was found that the apparent EP solubility increase (nearly twofold) observed at the highest NA concentration tested can be ascribed to a change in the polarity of the solvent mixture, rather than to a direct effect of NA on EP. The effect of fusion and re-crystallization from water or ethanol solutions on EP and NA mixtures was investigated by means of differential scanning calorimetry, elemental analysis and X-ray diffraction both on powder and single crystal. It was discovered that EP and NA form a co-crystal having a 1:1 molar composition that can be easily crystallized from ethanol. Single crystal X-ray analysis of this species revealed that the NA and EP molecules form corrugated layers within which the two components are intimately associated by a dense network of hydrogen bonds. In the presence of an excess NA in solution, the EP-NA co-crystal has lower water solubility with respect to both the single co-crystal formers and precipitates in aqueous solutions at ambient temperature.
The notion of controlled release has been known since the 1930s, but was not significantly develo... more The notion of controlled release has been known since the 1930s, but was not significantly developed until the 1970s. At that time, Alza introduced the concept of a "therapeutic system" and proposed new pharmaceutic formulations. Over time, the idea became one of controlled drug delivery and today concerns not only one rate of release but also the site of release of the active substance. We present here definitions, fundamentals and advantages and disadvantages of currently marketed systems and provide examples illustrating oral, transdermal and respiratory delivery systems. Current research is also examined.
A simple and sensitive HPLC method for the quantification of budesonide in skin layers was develo... more A simple and sensitive HPLC method for the quantification of budesonide in skin layers was developed and validated. Budesonide was extracted from stratum corneum, epidermis and dermis by means of a mixture of acetonitrile:water (recovery > 90%). Budesonide quantification was performed with a RP-C18 column using methanol and water mixture (69:31, v/v) as mobile phase, pumped at 0.8 ml/min. The absorbance was monitored at 254 nm. The method resulted to be selective, linear in the range 0.05-5 or 10 μg/ml, precise and accurate. LLOQ resulted to be 0.05 μg/ml. The developed method appeared to be appropriate for the quantification of budesonide in skin layers at the end of in vitro permeation experiments since the recovery of the applied dose was 97 ± 1%, in line with requirement of the OECD guideline for the testing of the chemicals (Skin absorption: in vitro method).
Estradiol transdermal application still represents a relevant topic due to the recent controversi... more Estradiol transdermal application still represents a relevant topic due to the recent controversies about hormone replacement therapy, its increasing potential in the treatment of skin aging and wound healing, and the new use of its derivatives in the transdermal contraceptive treatment. The aim of our work was to verify if fresh or frozen rabbit ear skin can be a suitable skin model to study in vitro estradiol transdermal absorption. Fresh rabbit ear skin demonstrated a reasonable model of human epidermis in the investigation of estradiol permeation starting from both solutions and commercial patches.
International Journal of Pharmaceutics, Feb 1, 2001
Triptorelin is a decapeptide analog of luteinizing hormone releasing hormone, currently used for ... more Triptorelin is a decapeptide analog of luteinizing hormone releasing hormone, currently used for the treatment of sex-hormones dependents diseases. The aim of this work was to prepare triptorelin-loaded nanospheres useful for transdermal iontophoretic administration. Nanospheres were prepared with the double emulsion/solvent evaporation technique. The effect of three parameters on the encapsulation efficiency has been determined: the role of the pH of the internal and external aqueous phases, the nature of the organic solvent and the effect of three different poly(lactide-co-glycolide) (PLGA) co-polymers. Particle size, zeta potential and release kinetics were also determined. The encapsulation efficiency varied from 4 to 83% reaching the maximum value when both the internal and the external water phases were brought to pH 7 (isoelectric point of the peptide), methylene chloride was used as solvent of the copolymers and PLGA rich in free carboxylic groups was employed. The release profiles obtained with this co-polymer were characterized by the absence of burst effect. This behavior as well as the high encapsulation efficiency was explained by an ionic interaction occurring between the peptide and the co-polymer. This supports the already expressed theory that the release of peptides and proteins from PLGA nanospheres is also governed by the affinity of the encapsulated molecule versus the polymer. The obtained nanoparticles, regarding their size, amount encapsulated and zeta potential, were shown to be suitable for transdermal iontophoretic administration.
Non-invasive drug delivery to the posterior segment of the eye represents an important unmet medi... more Non-invasive drug delivery to the posterior segment of the eye represents an important unmet medical need, and trans-scleral delivery could be an interesting solution. This review analyses the possibility of trans-scleral drug delivery for high molecular weight compounds, such as proteins and genetic material, which currently represent the most innovative and efficacious molecules for the treatment of many diseases of the posterior segment of the eye. The paper reviews all the barriers, both static and dynamic, involved in trans-scleral administration of drugs, trying to elucidate the role of each of them in the specific case of macromolecules. Delivery systems to sustain drug release and enhancing strategies to improve trans-scleral penetration are also described. Finally, the review approaches the use of computational models as a screening tool to evaluate the feasibility of trans-scleral administration for macromolecules.
Corticosteroids, although highly effective for the treatment of both anterior and posterior ocula... more Corticosteroids, although highly effective for the treatment of both anterior and posterior ocular segment inflammation, still nowadays struggle for effective drug delivery due to their poor solubilization capabilities in water. This research work aims to develop nanostructured lipid carriers (NLC) intended for periocular administration of dexamethasone acetate to the posterior segment of the eye. Pre-formulation studies were initially performed to find solid and liquid lipid mixtures for dexamethasone acetate solubilization. Pseudoternary diagrams at 65 °C were constructed to select the best surfactant based on the macroscopic transparency and microscopic isotropy of the systems. The resulting NLC, obtained following an organic solvent-free methodology, was composed of triacetin, Imwitor® 491 (glycerol monostearate >90%) and tyloxapol with Z-average = 106.9 ± 1.2 nm, PDI = 0.104 ± 0.019 and zeta potential = −6.51 ± 0.575 mV. Ex vivo porcine sclera and choroid permeation studies ...
This work aims at investigating the nicotinamide (NA)-ethyl-paraben (EP) binary system both in so... more This work aims at investigating the nicotinamide (NA)-ethyl-paraben (EP) binary system both in solution and in the solid state. In particular, the apparent EP solubility in water was studied in the presence of different NA concentrations (between 0.28 and 1.64 M). It was found that the apparent EP solubility increase (nearly twofold) observed at the highest NA concentration tested can be ascribed to a change in the polarity of the solvent mixture, rather than to a direct effect of NA on EP. The effect of fusion and re-crystallization from water or ethanol solutions on EP and NA mixtures was investigated by means of differential scanning calorimetry, elemental analysis and X-ray diffraction both on powder and single crystal. It was discovered that EP and NA form a co-crystal having a 1:1 molar composition that can be easily crystallized from ethanol. Single crystal X-ray analysis of this species revealed that the NA and EP molecules form corrugated layers within which the two components are intimately associated by a dense network of hydrogen bonds. In the presence of an excess NA in solution, the EP-NA co-crystal has lower water solubility with respect to both the single co-crystal formers and precipitates in aqueous solutions at ambient temperature.
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Papers by Sara Nicoli