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Papers by Paola Mura

Research paper thumbnail of Interaction of Naproxen with Alpha-Cyclodextrin and Its Noncyclic Analog Maltohexaose

Pharmaceutical Research, 1999

Purpose. To study the effect of mechanical grinding on crystallinity changes of naproxen (NAP) in... more Purpose. To study the effect of mechanical grinding on crystallinity changes of naproxen (NAP) in mixtures with a-cyclodextrin (aCd), amorphous aCd, and maltohexaose (M6); and the possible formation of a pseudo-inclusion complex between NAP and M6 in aqueous solution.

Research paper thumbnail of Development and optimization by experimental design of an in vitro method for prediction of drug buccal absorption

Research paper thumbnail of Physical–chemical characterization of binary and ternary systems of ketoprofen with cyclodextrins and phospholipids

Journal of Pharmaceutical and Biomedical Analysis, Dec 1, 2009

In the scope of improving the energy and power densities of electrochemical double layer capacito... more In the scope of improving the energy and power densities of electrochemical double layer capacitors (EDLCs), the development of high performance electrolytes with enhanced operative voltages is imperative. The formulation of mixtures containing ionic liquids with organic molecular solvents is an important strategy in the pursuit of developing highly electrochemically stable and safe materials while retaining fast transport properties for high power applications. In this work, we report on the physical−chemical investigations into binary mixtures containing the ionic liquid 1-butyl-1-methylpyrrolidinium bis{(trifluoromethyl)sulfonyl}imide with one mononitrile solvent, butyronitrile, and two dinitrile solvents, glutaronitrile and adiponitrile, as potential electrolytes for EDLCs. The thermal, volumetric, and transport properties of the binary mixtures are investigated as functions of the electrolyte composition and temperature. Furthermore, the electrolyte composition which exhibits the highest conductivity for each of the binary mixtures was determined, and its electrochemical stability is reported using a glassy carbon macrodisk electrode.

Research paper thumbnail of Response surface methodology in the optimization of chitosan–Ca pectinate bead formulations

European Journal of Pharmaceutical Sciences, Nov 1, 2008

This study describes the application of a multi-varied experimental design methodology to the opt... more This study describes the application of a multi-varied experimental design methodology to the optimization of a bead formulation based on a mixed network of Ca pectinate and chitosan. The effect of varying the relative percent of the three components used for the bead production, i.e. pectin, chitosan and CaCl2, has been systematically investigated with the aim of identifying their best

Research paper thumbnail of Preparation and solid-state characterization of bupivacaine hydrochloride cyclodextrin complexes aimed for buccal delivery

Journal of Pharmaceutical and Biomedical Analysis, May 1, 2010

Binary products of bupivacaine hydrochloride (BVP HCl), an amide type local anesthetic, with pare... more Binary products of bupivacaine hydrochloride (BVP HCl), an amide type local anesthetic, with parent beta-cyclodextrin (beta-CD) and its soluble beta-cyclodextrin-epichlorohydrin polymer (EPI-beta-CD) were prepared and evaluated as a first phase in the development of a novel mucoadhesive formulation aimed for buccal delivery of this drug. The solid products were obtained by physical mixing, ball milling in high-energy mills, co-evaporation and lyophilisation, in order to rationally select the most effective preparation technique. The solid products obtained were carefully characterised by differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier transform infrared spectroscopy (FTIR) and environmental scanning electron microscopy (ESEM). The impact of the preparation techniques on the physicochemical properties of plain drug was also studied. Results of solid-state analysis revealed more intense interactions of BVP HCl with EPI-beta-CD than with native beta-CD, accompanied by stronger reduction of drug crystallinity in the samples, probably favoured by the amorphous nature of the polymeric carrier. While summarising the results of DSC and XRPD analyses, it seems that ball milling of drug/cyclodextrin binary mixtures was particularly efficient in inducing solid-state interaction between the components and it can be considered as the method of choice for preparation of complexes of BVP HCl with beta-CD and EPI-beta-CD. In vitro dissolution properties in artificial saliva of ball-milled BVP HCl and corresponding CD complexes were investigated by simulating the conditions present at the surface of the buccal mucosa. The obtained results confirmed that complexation of BVP HCl with beta-CD and EPI-beta-CD is a suitable tool for properly tailoring the dissolution properties of the drug and it can be favourably exploited for the development of an effective buccal drug delivery system.

Research paper thumbnail of Advanced formulations for improving therapies with anti-inflammatory or anaesthetic drugs: A review

Journal of Drug Delivery Science and Technology, Apr 1, 2016

Abstract The development of new more effective therapeutic treatments for pain relief is essentia... more Abstract The development of new more effective therapeutic treatments for pain relief is essential for enhancing the patient quality of life and safety and avoiding or limiting risks of abuse, addiction or serious injuries posed by some of the present pain therapies. With this aim, in the last years, several advanced delivery systems have been developed to increase bioavailability, therapeutic efficacy and safety of well known analgesics, overcoming limits and drawbacks of traditional formulations. Among the different kinds of drugs used in the treatment of pain, non-opioid drugs such as local anaesthetics, corticosteroids and non steroidal anti-inflammatory drugs are preferred in the treatment of mild or moderate pain. However, each of these classes is associated with different adverse events and inconveniences, most of which could be reduced or overcome by appropriate drug carrier systems. This review is focused on recent drug delivery strategies based on micro- and nano-technologies developed for improving the effectiveness in pain management through non-opioid agents, exploiting different approaches such as: cyclodextrin complexation, solid dispersions with hydrophilic polymers, mechano-chemically activated systems, micro and nanoparticles, micro and nano-emulsions, vesicular systems. Combined approaches, simultaneously exploiting the relative advantages of such systems in a single drug delivery device, were also reviewed.

Research paper thumbnail of Development and characterization of functionalized niosomes for brain targeting of dynorphin-B

European Journal of Pharmaceutics and Biopharmaceutics, May 1, 2014

ABSTRACT A niosomal formulation, functionalized with N-palmitoylglucosamine, was developed as pot... more ABSTRACT A niosomal formulation, functionalized with N-palmitoylglucosamine, was developed as potential brain targeted delivery system of dynorphin-B. In fact, this endogenous neuropeptide, selective agonist of k opioid receptors, is endowed with relevant pharmacological activities on the central nervous system, including a marked antinociceptive effect, but is unable to cross the blood brain barrier (BBB), thus requiring intracerebroventricular administration. Statistical design of experiments was utilized for a systematic evaluation of the influence of variations of the relative amounts of the components of the vesicle membrane (Span 60, cholesterol and Solulan C24) on vesicle mean diameter, polydispersity index and drug entrapment efficiency, chosen as the responses to optimize. A Scheffé simplex-centroid design was used to obtain the coefficients of the postulated mathematical model. The study of the response surface plots revealed that variations of the considered factors had different effects on the selected responses. The desirability function enabled for finding the optimal mixture composition, which represented the best compromise to simultaneously optimize all the three responses. The experimental values obtained with the optimized formulation were very similar to the predicted ones, proving the validity of the proposed regression model. The optimized niosomal formulation of dynorphin-B administered intravenously to mice (100 mg/Kg) showed a pronounced antinociceptive effect, significantly higher (P<0.05) than that given by i.v. administration of the simple solution of the peptide at the same concentration, proving its effectiveness in enabling the peptide brain delivery. These positive results suggest that the proposed approach could be successfully extended to other neuro-active peptides exerting a strong central action, even at low doses, but unable to cross the BBB.

Research paper thumbnail of Hybrid systems based on “drug – in cyclodextrin – in nanoclays” for improving oxaprozin dissolution properties

International Journal of Pharmaceutics, Jul 1, 2016

A combined approach based on drug complexation with cyclodextrins, and complex entrapment in nano... more A combined approach based on drug complexation with cyclodextrins, and complex entrapment in nanoclays has been investigated, to join in a single delivery system the benefits of these carriers and potentiate their ability to improve the dissolution properties of oxaprozin (OXA), a poorly water-soluble anti-inflammatory drug. Based on previous studies, randomly methylated ß-cyclodextrin (RAMEB) was chosen as the most effective cyclodextrin for OXA complexation. Adsorption equilibrium studies performed on three different clays (sepiolite, attapulgite, bentonite) allowed selection of sepiolite (SV) for its greater adsorption power towards OXA. DSC and XRPD studies indicated drug amorphization in both binary OXA-RAMEB coground and OXA-SV cofused products, due to its complexation or very fine dispersion in the clay structure, respectively. The drug amorphous state was maintained also in the ternary OXA-RAMEB-SV cofused system. Dissolution studies evidenced a clear synergistic effect of RAMEB complexation and clay nanoencapsulation in improving the OXA dissolution properties, with an almost 100% increase in percent dissolved and dissolution efficiency compared to the OXA-RAMEB coground system. Therefore, the proposed combined approach represents an interesting tool for improving the therapeutic effectiveness of poorly soluble drugs, and reducing the CD amount necessary for obtaining the desired drug solubility and dissolution rate increase.

Research paper thumbnail of Design, Evaluation and Comparison of Nanostructured Lipid Carriers and Chitosan Nanoparticles as Carriers of Poorly Soluble Drugs to Develop Oral Liquid Formulations Suitable for Pediatric Use

Pharmaceutics, Apr 21, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Development of mucoadhesive wafers loaded with econazole-cyclodextrin complexes for treatment of oral candidiadis

Research paper thumbnail of Development and Characterization of Cyclodextrin-Based Nanogels as a New Ibuprofen Cutaneous Delivery System

Pharmaceutics, Nov 23, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Effect of preparation technique on the properties and in vivo efficacy of benzocaine-loaded ethosomes

Journal of Liposome Research, 2009

... Francesca Maestrelli 1 , Gaetano Capasso 1 , Maria L. González-Rodríguez 2 , Antonio M. Rabas... more ... Francesca Maestrelli 1 , Gaetano Capasso 1 , Maria L. González-Rodríguez 2 , Antonio M. Rabasco 2 , Carla Ghelardini 3 , Paola Mura 1 1 Department of Pharmaceutical Sciences, University of Florence, Italy. ... Dubey V, Mishra D, Dutta T, Nahar M, Saraf DK, Jain NK. (2007). ...

Research paper thumbnail of Development of a Hydroxypropyl-β-Cyclodextrin-Based Liquid Formulation for the Oral Administration of Propranolol in Pediatric Therapy

Pharmaceutics

Propranolol (PPN) is widely used in children to treat various cardiovascular diseases. The availa... more Propranolol (PPN) is widely used in children to treat various cardiovascular diseases. The availability of a suitable PPN solution should avoid recourse to extemporaneous preparations of unknown/limited stability, as commonly made in hospital pharmacies. However, the development of pediatric PPN solutions is hindered by their instability to light and stability at pH ≈ 3, bitter taste, and the need to improve palatability and avoid co-solvents, flavoring agents, or preservatives that are potentially toxic. In this study, cyclodextrin (CD) complexation has been exploited to develop a safe, stable, and palatable oral pediatric solution of PPN. An initial screening among various CDs allowed us to select HPβCD for its good complexing ability and no toxicity. Drug-HPβCD physical mixtures or co-ground systems (1:1 or 1:2 mol:mol) were used to prepare 0.2% w/v drug solutions. Photo stability studies evidenced the protective effect of HPβCD, revealing a reduction of up to 75% in the drug deg...

Research paper thumbnail of Development and Characterization of Cyclodextrin-Based Nanogels as a New Ibuprofen Cutaneous Delivery System

Pharmaceutics

Nanogels combine the properties of hydrogels and nanocarrier systems, resulting in very effective... more Nanogels combine the properties of hydrogels and nanocarrier systems, resulting in very effective drug delivery systems, including for cutaneous applications. Cyclodextrins (CDs) have been utilised to enhance the nanogels’ loading ability towards poorly soluble drugs and promote/sustain drug release. However, formation of CD-based nanogels requires the use of specially modified CDs, or of crosslinking agents. The aim of this work was to develop a CD-based nanogel to improve the cutaneous delivery of ibuprofen by using the soluble β-cyclodextrin/epichlorohydrin polymer (EPIβCD) without adding any potentially toxic crosslinker. The use of EPIβCD enabled increasing ibuprofen loading due to its complexing/solubilizing power towards the poorly soluble drug and prolonging drug release over time due to the nanogel formation. DLS analysis proved that EPIβCD allowed the formation of nanostructures ranging from 60 up to 400 nm, depending on the gelling agent type and the gel preparation metho...

Research paper thumbnail of Design, Evaluation and Comparison of Nanostructured Lipid Carriers and Chitosan Nanoparticles as Carriers of Poorly Soluble Drugs to Develop Oral Liquid Formulations Suitable for Pediatric Use

Pharmaceutics

There is a serious need of pediatric drug formulations, whose lack causes the frequent use of ext... more There is a serious need of pediatric drug formulations, whose lack causes the frequent use of extemporaneous preparations obtained from adult dosage forms, with consequent safety and quality risks. Oral solutions are the best choice for pediatric patients, due to administration ease and dosage-adaptability, but their development is challenging, particularly for poorly soluble drugs. In this work, chitosan nanoparticles (CSNPs) and nanostructured lipid carriers (NLCs) were developed and evaluated as potential nanocarriers for preparing oral pediatric solutions of cefixime (poorly soluble model drug). The selected CSNPs and NLCs showed a size around 390 nm, Zeta-potential > 30 mV, and comparable entrapment efficiency (31–36%), but CSNPs had higher loading efficiency (5.2 vs. 1.4%). CSNPs maintained an almost unchanged size, homogeneity, and Zeta-potential during storage, while NLCs exhibited a marked progressive Zeta-potential decrease. Drug release from CSNPs formulations (differe...

Research paper thumbnail of The influence of pH and water-soluble polymers on naproxen cyclodextrin complexation

Research paper thumbnail of Quality by design in the optimization of a nanosystem-ethosomal formulation for topical treatment of vitiligo

Research paper thumbnail of Development of pectine-based mucoadhesive patches for buccal delivery of triclosan: effect of cyclodextrin complexation

Elimination of cariogenic bacteria from dental film is an important step in prevention and treatm... more Elimination of cariogenic bacteria from dental film is an important step in prevention and treatment of dental conditions and of related systemic diseases. Triclosan (TR), a broad spectrum antibacterial agent, is a possible candidate for this aim. However, to obtain effective TR levels in the oral cavity, there is the need of developing a suitable formulation allowing both a prolonged in situ residence and a controlled drug release. The design of such formulation is a particularly challenging issue for a poorly soluble drug as TR, due to the limited amount of saliva in the mouth, acting as dissolution medium. Based on these premises, we considered it worthy of interest to develop a TR mucoadhesive buccal formulation, by using pectin-Carbopol combinations as mucoadhesive matrix-forming polymer, and exploiting cyclodextrin (CD) complexation (with polymeric or native sCD) for improving drug solubility and optimising its release rate from the matrix. Phase-solubility studies were perfor...

Research paper thumbnail of Development and microbiological evaluation of chitosan and chitosan-alginate microspheres for vaginal administration of metronidazole

International Journal of Pharmaceutics, 2021

Metronidazole is the drug of choice in the treatment of bacterial vaginosis, but the oral therapy... more Metronidazole is the drug of choice in the treatment of bacterial vaginosis, but the oral therapy can induce several collateral effects. Aim of this work was the development of a vaginal multiparticulate system loaded with metronidazole able to improve its residence time allowing a complete drug release. Several kinds of MS were prepared using chitosan dissolved in different organic acids or alginate coated with chitosan. FTIR and DSC analyses were performed to study the interactions between the drug and the polymers, while MS morphology was investigated with optical and electron microscopy. All the formulations were characterized in terms of drug entrapment efficiency, mucoadhesion, swelling capacity and drug release behavior, demonstrating the best results for alginate MS coated with chitosan. The formulations evidenced a complete and rapid release of drug, compared with the commercial form: Zidoval®.The best formulations assayed for antibacterial activity confirmed the suitability of this new formulation for the vaginal treatment of local diseases.

Research paper thumbnail of A preliminary study for the development and optimization by experimental design of an in vitro method for prediction of drug buccal absorption

International Journal of Pharmaceutics, 2018

The work was aimed at developing an in vitro method able to provide rapid and reliable evaluation... more The work was aimed at developing an in vitro method able to provide rapid and reliable evaluation of drug absorption through buccal mucosa. Absorption simulator apparatus endowed with an artificial membrane was purposely developed by experimental design. The apparent permeation coefficient (P app) through excised porcine buccal mucosa of naproxen, selected as model drug, was the target value to obtain with the artificial membrane. The multivariate approach enabled systematic evaluation of the effect on the response (P app) of simultaneous variations of the variables (kind of lipid components for support impregnation and relative amounts). A screening phase followed by a response-surface study allowed optimization of the lipid-mixture composition to obtain the desired P app value, and definition of a design space where all mixture components combinations fulfilled the desired target at a fixed probability level. The method offers a useful tool for a quick screening in the early stages of drug discovery and/or in preformulation studies, improving efficiency and chance of success in the development of buccal delivery systems. Further studies with other model drugs are planned to confirm the buccal absorption predictive capacity of the developed membrane.

Research paper thumbnail of Interaction of Naproxen with Alpha-Cyclodextrin and Its Noncyclic Analog Maltohexaose

Pharmaceutical Research, 1999

Purpose. To study the effect of mechanical grinding on crystallinity changes of naproxen (NAP) in... more Purpose. To study the effect of mechanical grinding on crystallinity changes of naproxen (NAP) in mixtures with a-cyclodextrin (aCd), amorphous aCd, and maltohexaose (M6); and the possible formation of a pseudo-inclusion complex between NAP and M6 in aqueous solution.

Research paper thumbnail of Development and optimization by experimental design of an in vitro method for prediction of drug buccal absorption

Research paper thumbnail of Physical–chemical characterization of binary and ternary systems of ketoprofen with cyclodextrins and phospholipids

Journal of Pharmaceutical and Biomedical Analysis, Dec 1, 2009

In the scope of improving the energy and power densities of electrochemical double layer capacito... more In the scope of improving the energy and power densities of electrochemical double layer capacitors (EDLCs), the development of high performance electrolytes with enhanced operative voltages is imperative. The formulation of mixtures containing ionic liquids with organic molecular solvents is an important strategy in the pursuit of developing highly electrochemically stable and safe materials while retaining fast transport properties for high power applications. In this work, we report on the physical−chemical investigations into binary mixtures containing the ionic liquid 1-butyl-1-methylpyrrolidinium bis{(trifluoromethyl)sulfonyl}imide with one mononitrile solvent, butyronitrile, and two dinitrile solvents, glutaronitrile and adiponitrile, as potential electrolytes for EDLCs. The thermal, volumetric, and transport properties of the binary mixtures are investigated as functions of the electrolyte composition and temperature. Furthermore, the electrolyte composition which exhibits the highest conductivity for each of the binary mixtures was determined, and its electrochemical stability is reported using a glassy carbon macrodisk electrode.

Research paper thumbnail of Response surface methodology in the optimization of chitosan–Ca pectinate bead formulations

European Journal of Pharmaceutical Sciences, Nov 1, 2008

This study describes the application of a multi-varied experimental design methodology to the opt... more This study describes the application of a multi-varied experimental design methodology to the optimization of a bead formulation based on a mixed network of Ca pectinate and chitosan. The effect of varying the relative percent of the three components used for the bead production, i.e. pectin, chitosan and CaCl2, has been systematically investigated with the aim of identifying their best

Research paper thumbnail of Preparation and solid-state characterization of bupivacaine hydrochloride cyclodextrin complexes aimed for buccal delivery

Journal of Pharmaceutical and Biomedical Analysis, May 1, 2010

Binary products of bupivacaine hydrochloride (BVP HCl), an amide type local anesthetic, with pare... more Binary products of bupivacaine hydrochloride (BVP HCl), an amide type local anesthetic, with parent beta-cyclodextrin (beta-CD) and its soluble beta-cyclodextrin-epichlorohydrin polymer (EPI-beta-CD) were prepared and evaluated as a first phase in the development of a novel mucoadhesive formulation aimed for buccal delivery of this drug. The solid products were obtained by physical mixing, ball milling in high-energy mills, co-evaporation and lyophilisation, in order to rationally select the most effective preparation technique. The solid products obtained were carefully characterised by differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier transform infrared spectroscopy (FTIR) and environmental scanning electron microscopy (ESEM). The impact of the preparation techniques on the physicochemical properties of plain drug was also studied. Results of solid-state analysis revealed more intense interactions of BVP HCl with EPI-beta-CD than with native beta-CD, accompanied by stronger reduction of drug crystallinity in the samples, probably favoured by the amorphous nature of the polymeric carrier. While summarising the results of DSC and XRPD analyses, it seems that ball milling of drug/cyclodextrin binary mixtures was particularly efficient in inducing solid-state interaction between the components and it can be considered as the method of choice for preparation of complexes of BVP HCl with beta-CD and EPI-beta-CD. In vitro dissolution properties in artificial saliva of ball-milled BVP HCl and corresponding CD complexes were investigated by simulating the conditions present at the surface of the buccal mucosa. The obtained results confirmed that complexation of BVP HCl with beta-CD and EPI-beta-CD is a suitable tool for properly tailoring the dissolution properties of the drug and it can be favourably exploited for the development of an effective buccal drug delivery system.

Research paper thumbnail of Advanced formulations for improving therapies with anti-inflammatory or anaesthetic drugs: A review

Journal of Drug Delivery Science and Technology, Apr 1, 2016

Abstract The development of new more effective therapeutic treatments for pain relief is essentia... more Abstract The development of new more effective therapeutic treatments for pain relief is essential for enhancing the patient quality of life and safety and avoiding or limiting risks of abuse, addiction or serious injuries posed by some of the present pain therapies. With this aim, in the last years, several advanced delivery systems have been developed to increase bioavailability, therapeutic efficacy and safety of well known analgesics, overcoming limits and drawbacks of traditional formulations. Among the different kinds of drugs used in the treatment of pain, non-opioid drugs such as local anaesthetics, corticosteroids and non steroidal anti-inflammatory drugs are preferred in the treatment of mild or moderate pain. However, each of these classes is associated with different adverse events and inconveniences, most of which could be reduced or overcome by appropriate drug carrier systems. This review is focused on recent drug delivery strategies based on micro- and nano-technologies developed for improving the effectiveness in pain management through non-opioid agents, exploiting different approaches such as: cyclodextrin complexation, solid dispersions with hydrophilic polymers, mechano-chemically activated systems, micro and nanoparticles, micro and nano-emulsions, vesicular systems. Combined approaches, simultaneously exploiting the relative advantages of such systems in a single drug delivery device, were also reviewed.

Research paper thumbnail of Development and characterization of functionalized niosomes for brain targeting of dynorphin-B

European Journal of Pharmaceutics and Biopharmaceutics, May 1, 2014

ABSTRACT A niosomal formulation, functionalized with N-palmitoylglucosamine, was developed as pot... more ABSTRACT A niosomal formulation, functionalized with N-palmitoylglucosamine, was developed as potential brain targeted delivery system of dynorphin-B. In fact, this endogenous neuropeptide, selective agonist of k opioid receptors, is endowed with relevant pharmacological activities on the central nervous system, including a marked antinociceptive effect, but is unable to cross the blood brain barrier (BBB), thus requiring intracerebroventricular administration. Statistical design of experiments was utilized for a systematic evaluation of the influence of variations of the relative amounts of the components of the vesicle membrane (Span 60, cholesterol and Solulan C24) on vesicle mean diameter, polydispersity index and drug entrapment efficiency, chosen as the responses to optimize. A Scheffé simplex-centroid design was used to obtain the coefficients of the postulated mathematical model. The study of the response surface plots revealed that variations of the considered factors had different effects on the selected responses. The desirability function enabled for finding the optimal mixture composition, which represented the best compromise to simultaneously optimize all the three responses. The experimental values obtained with the optimized formulation were very similar to the predicted ones, proving the validity of the proposed regression model. The optimized niosomal formulation of dynorphin-B administered intravenously to mice (100 mg/Kg) showed a pronounced antinociceptive effect, significantly higher (P<0.05) than that given by i.v. administration of the simple solution of the peptide at the same concentration, proving its effectiveness in enabling the peptide brain delivery. These positive results suggest that the proposed approach could be successfully extended to other neuro-active peptides exerting a strong central action, even at low doses, but unable to cross the BBB.

Research paper thumbnail of Hybrid systems based on “drug – in cyclodextrin – in nanoclays” for improving oxaprozin dissolution properties

International Journal of Pharmaceutics, Jul 1, 2016

A combined approach based on drug complexation with cyclodextrins, and complex entrapment in nano... more A combined approach based on drug complexation with cyclodextrins, and complex entrapment in nanoclays has been investigated, to join in a single delivery system the benefits of these carriers and potentiate their ability to improve the dissolution properties of oxaprozin (OXA), a poorly water-soluble anti-inflammatory drug. Based on previous studies, randomly methylated ß-cyclodextrin (RAMEB) was chosen as the most effective cyclodextrin for OXA complexation. Adsorption equilibrium studies performed on three different clays (sepiolite, attapulgite, bentonite) allowed selection of sepiolite (SV) for its greater adsorption power towards OXA. DSC and XRPD studies indicated drug amorphization in both binary OXA-RAMEB coground and OXA-SV cofused products, due to its complexation or very fine dispersion in the clay structure, respectively. The drug amorphous state was maintained also in the ternary OXA-RAMEB-SV cofused system. Dissolution studies evidenced a clear synergistic effect of RAMEB complexation and clay nanoencapsulation in improving the OXA dissolution properties, with an almost 100% increase in percent dissolved and dissolution efficiency compared to the OXA-RAMEB coground system. Therefore, the proposed combined approach represents an interesting tool for improving the therapeutic effectiveness of poorly soluble drugs, and reducing the CD amount necessary for obtaining the desired drug solubility and dissolution rate increase.

Research paper thumbnail of Design, Evaluation and Comparison of Nanostructured Lipid Carriers and Chitosan Nanoparticles as Carriers of Poorly Soluble Drugs to Develop Oral Liquid Formulations Suitable for Pediatric Use

Pharmaceutics, Apr 21, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Development of mucoadhesive wafers loaded with econazole-cyclodextrin complexes for treatment of oral candidiadis

Research paper thumbnail of Development and Characterization of Cyclodextrin-Based Nanogels as a New Ibuprofen Cutaneous Delivery System

Pharmaceutics, Nov 23, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Research paper thumbnail of Effect of preparation technique on the properties and in vivo efficacy of benzocaine-loaded ethosomes

Journal of Liposome Research, 2009

... Francesca Maestrelli 1 , Gaetano Capasso 1 , Maria L. González-Rodríguez 2 , Antonio M. Rabas... more ... Francesca Maestrelli 1 , Gaetano Capasso 1 , Maria L. González-Rodríguez 2 , Antonio M. Rabasco 2 , Carla Ghelardini 3 , Paola Mura 1 1 Department of Pharmaceutical Sciences, University of Florence, Italy. ... Dubey V, Mishra D, Dutta T, Nahar M, Saraf DK, Jain NK. (2007). ...

Research paper thumbnail of Development of a Hydroxypropyl-β-Cyclodextrin-Based Liquid Formulation for the Oral Administration of Propranolol in Pediatric Therapy

Pharmaceutics

Propranolol (PPN) is widely used in children to treat various cardiovascular diseases. The availa... more Propranolol (PPN) is widely used in children to treat various cardiovascular diseases. The availability of a suitable PPN solution should avoid recourse to extemporaneous preparations of unknown/limited stability, as commonly made in hospital pharmacies. However, the development of pediatric PPN solutions is hindered by their instability to light and stability at pH ≈ 3, bitter taste, and the need to improve palatability and avoid co-solvents, flavoring agents, or preservatives that are potentially toxic. In this study, cyclodextrin (CD) complexation has been exploited to develop a safe, stable, and palatable oral pediatric solution of PPN. An initial screening among various CDs allowed us to select HPβCD for its good complexing ability and no toxicity. Drug-HPβCD physical mixtures or co-ground systems (1:1 or 1:2 mol:mol) were used to prepare 0.2% w/v drug solutions. Photo stability studies evidenced the protective effect of HPβCD, revealing a reduction of up to 75% in the drug deg...

Research paper thumbnail of Development and Characterization of Cyclodextrin-Based Nanogels as a New Ibuprofen Cutaneous Delivery System

Pharmaceutics

Nanogels combine the properties of hydrogels and nanocarrier systems, resulting in very effective... more Nanogels combine the properties of hydrogels and nanocarrier systems, resulting in very effective drug delivery systems, including for cutaneous applications. Cyclodextrins (CDs) have been utilised to enhance the nanogels’ loading ability towards poorly soluble drugs and promote/sustain drug release. However, formation of CD-based nanogels requires the use of specially modified CDs, or of crosslinking agents. The aim of this work was to develop a CD-based nanogel to improve the cutaneous delivery of ibuprofen by using the soluble β-cyclodextrin/epichlorohydrin polymer (EPIβCD) without adding any potentially toxic crosslinker. The use of EPIβCD enabled increasing ibuprofen loading due to its complexing/solubilizing power towards the poorly soluble drug and prolonging drug release over time due to the nanogel formation. DLS analysis proved that EPIβCD allowed the formation of nanostructures ranging from 60 up to 400 nm, depending on the gelling agent type and the gel preparation metho...

Research paper thumbnail of Design, Evaluation and Comparison of Nanostructured Lipid Carriers and Chitosan Nanoparticles as Carriers of Poorly Soluble Drugs to Develop Oral Liquid Formulations Suitable for Pediatric Use

Pharmaceutics

There is a serious need of pediatric drug formulations, whose lack causes the frequent use of ext... more There is a serious need of pediatric drug formulations, whose lack causes the frequent use of extemporaneous preparations obtained from adult dosage forms, with consequent safety and quality risks. Oral solutions are the best choice for pediatric patients, due to administration ease and dosage-adaptability, but their development is challenging, particularly for poorly soluble drugs. In this work, chitosan nanoparticles (CSNPs) and nanostructured lipid carriers (NLCs) were developed and evaluated as potential nanocarriers for preparing oral pediatric solutions of cefixime (poorly soluble model drug). The selected CSNPs and NLCs showed a size around 390 nm, Zeta-potential > 30 mV, and comparable entrapment efficiency (31–36%), but CSNPs had higher loading efficiency (5.2 vs. 1.4%). CSNPs maintained an almost unchanged size, homogeneity, and Zeta-potential during storage, while NLCs exhibited a marked progressive Zeta-potential decrease. Drug release from CSNPs formulations (differe...

Research paper thumbnail of The influence of pH and water-soluble polymers on naproxen cyclodextrin complexation

Research paper thumbnail of Quality by design in the optimization of a nanosystem-ethosomal formulation for topical treatment of vitiligo

Research paper thumbnail of Development of pectine-based mucoadhesive patches for buccal delivery of triclosan: effect of cyclodextrin complexation

Elimination of cariogenic bacteria from dental film is an important step in prevention and treatm... more Elimination of cariogenic bacteria from dental film is an important step in prevention and treatment of dental conditions and of related systemic diseases. Triclosan (TR), a broad spectrum antibacterial agent, is a possible candidate for this aim. However, to obtain effective TR levels in the oral cavity, there is the need of developing a suitable formulation allowing both a prolonged in situ residence and a controlled drug release. The design of such formulation is a particularly challenging issue for a poorly soluble drug as TR, due to the limited amount of saliva in the mouth, acting as dissolution medium. Based on these premises, we considered it worthy of interest to develop a TR mucoadhesive buccal formulation, by using pectin-Carbopol combinations as mucoadhesive matrix-forming polymer, and exploiting cyclodextrin (CD) complexation (with polymeric or native sCD) for improving drug solubility and optimising its release rate from the matrix. Phase-solubility studies were perfor...

Research paper thumbnail of Development and microbiological evaluation of chitosan and chitosan-alginate microspheres for vaginal administration of metronidazole

International Journal of Pharmaceutics, 2021

Metronidazole is the drug of choice in the treatment of bacterial vaginosis, but the oral therapy... more Metronidazole is the drug of choice in the treatment of bacterial vaginosis, but the oral therapy can induce several collateral effects. Aim of this work was the development of a vaginal multiparticulate system loaded with metronidazole able to improve its residence time allowing a complete drug release. Several kinds of MS were prepared using chitosan dissolved in different organic acids or alginate coated with chitosan. FTIR and DSC analyses were performed to study the interactions between the drug and the polymers, while MS morphology was investigated with optical and electron microscopy. All the formulations were characterized in terms of drug entrapment efficiency, mucoadhesion, swelling capacity and drug release behavior, demonstrating the best results for alginate MS coated with chitosan. The formulations evidenced a complete and rapid release of drug, compared with the commercial form: Zidoval®.The best formulations assayed for antibacterial activity confirmed the suitability of this new formulation for the vaginal treatment of local diseases.

Research paper thumbnail of A preliminary study for the development and optimization by experimental design of an in vitro method for prediction of drug buccal absorption

International Journal of Pharmaceutics, 2018

The work was aimed at developing an in vitro method able to provide rapid and reliable evaluation... more The work was aimed at developing an in vitro method able to provide rapid and reliable evaluation of drug absorption through buccal mucosa. Absorption simulator apparatus endowed with an artificial membrane was purposely developed by experimental design. The apparent permeation coefficient (P app) through excised porcine buccal mucosa of naproxen, selected as model drug, was the target value to obtain with the artificial membrane. The multivariate approach enabled systematic evaluation of the effect on the response (P app) of simultaneous variations of the variables (kind of lipid components for support impregnation and relative amounts). A screening phase followed by a response-surface study allowed optimization of the lipid-mixture composition to obtain the desired P app value, and definition of a design space where all mixture components combinations fulfilled the desired target at a fixed probability level. The method offers a useful tool for a quick screening in the early stages of drug discovery and/or in preformulation studies, improving efficiency and chance of success in the development of buccal delivery systems. Further studies with other model drugs are planned to confirm the buccal absorption predictive capacity of the developed membrane.