Bice Conti

Bioadhesive Microspheres for Ophthalmic Administration of Acyclovir

The bioavailability of acyclovir to the ophthalmic epithelium is low and when the drug is administered in ophthalmic ointment it must be applied every four hours. An emulsification technique has been used to prepare acyclovir‐loaded chitosan microspheres with the aim of promoting the prolonged release of drug and increasing its ocular bioavailability.

Gamma irradiation effects on poly(dl-lactictide-co-glycolide) microspheres

Gamma radiation treatment plays an increasingly important role in the sterilization/sanitization of pharmaceutical products. However, irradiation may affect the stability of the product and thus its safety of use. We investigated the influence of ionizing radiation on modified release microparticulate drug delivery systems made of two types of polylactide-co-glycolide copolymers (PLG): RG 503 and RG 503H; these polymers have identical molecular weights but different chemical structures. The effect of gamma radiation on polymer stability of the raw polymers (P) and related microspheres (Ms) was evaluated. Samples were irradiated at different irradiation doses (5, 15 and 25 kGy) using 60Co as radiation source. The microspheres were prepared using the spray drying technique. Degradation of PLG and related microspheres was evaluated during six months in terms of average molecular weight (Mw) loss by gel permeation chromatography (GPC) and variation in glass transition temperature (Tg) using differential calorimetry (DSC). The presence of free radicals in the product was tested by electron paramagnetic resonance (EPR). Both P and Ms showed a trend in decreasing their Mw at time 0 as a function of irradiation dose. For RG503 the decay in Mw is always negligible for doses below 15 kGy while it is about 10% for 25 kGy. After 150 days Mw decay was 25% in the microspheres and 20% in the raw polymer. It was not possible to evaluate the radiation effect, at different storage times, for RG503H because this polymer resulted to be unstable even in the regular storage conditions without being irradiated. The concentration of radiation-induced free radicals was higher in RG 503H (both P and Ms) and they were more stable than the free radicals species observed in the case of polymer RG 503. Alterations and/or production of new radicals were observed on exposure of RG 503H microspheres to the light. Radiolytic degradation of RG 503 under vacuum is characterized by a prevalence of the chain scission events leading to a decrease of Mw. Some crosslinking can occur mainly in the post irradiation stage through the decay and coupling of the hydrogen abstraction radicals. A hydroperoxydative cycle, whose mechanism is suggested, is generated in the presence of oxygen.

Preparation and characterization of ampicillin loaded methylpyrrolidinone chitosan and chitosan microspheres

Ampicillin was embedded in microparticles made of a new derivative of chitosan: methylpyrrolidinone chitosan. They were prepared using different drug-to-polymer weight ratios and by a spray-drying technique. Spray-dried drug-loaded chitosan microspheres were prepared for comparison. The microparticles were characterized by scanning electron microscopy (SEM), particle size analysis, differential scanning calorimetry (DSC) and in vitro drug release. Microbiological assay was performed using different bacterial strains. Spray-dried microspheres of almost spherical shape, smooth surface and narrow size distribution were always obtained. Ampicillin loaded into both polymer matrices showed amorphous behaviour as determined by DSC. Drug-loaded microspheres resulted to control the drug release in a 30-120 min range, depending on chitosan type. Thermal denaturation of the microspheres does not modify drug release rate. The results of the microbiological assay show that the loading of ampicillin into chitosans is able to maintain or improve the anti-bacterial activity of the drug.

Influence of glutaraldehyde on drug release and mucoadhesive properties of chitosan microspheres

Abstract Among bioadhesive drug delivery systems, chitosan microspheres can be considered useful formulations for mucosal administration of drugs. The feasibility of modulating drug release from chitosan microparticles is due to polymer cross-linking, i.e. by glutaraldehyde. The aim of this work was to develop a new simple ‘in vitro’ technique based on electron microscopy in order to study the effect of polymer crosslinking density on mucoadhesive properties of the chitosan microspheres. This technique consists of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations on morphological changes of chitosan microspheres with various cross-linking densities in contact with mucin solution. The results of SEM and TEM analyses have permitted to confirm the high affinity for mucin of uncross-linked chitosan microspheres and thus their bioadhesive properties. Moreover, bioadhesive characteristics of the microparticulate drug delivery systems were depressed for glutaraldehyde cross-linked chitosan microspheres.

Use of polylactic acid for the preparation of microparticulate drug delivery systems

This report reviews the development of particulate drug delivery systems technology based on polylactic acid (PLA). The following methods used to produce PLA microparticles are considered: emulsion solvent evaporation, emulsion solvent extraction, interfacial phase deposition, spray coating, and the melting method. The different preparation processes and parameters used, the characteristics of microparticles obtained and those parameters affecting the characteristics of these systems, are discussed.

Study on glycolic acid delivery by liposomes and microspheres

Glycolic acid is used in many cosmetic products as exfoliant and moisturizer. Unfortunately, the greater glycolic acid cosmetic benefits the greater is the potential for skin irritation as far as burning. The aim of this work was to investigate the feasibility of topical controlled delivery systems loading glycolic acid in order to optimize the acid cosmetic properties lowering its side effects. For this purpose different types of microparticulate systems have been evaluated: liposomes, liposomes modified by chitosan addition and chitosan microspheres. Liposomes, composed of phosphatidylcholine and cholesterol (1:1 molar ratio) and with different glycolic acid/lipid molar ratio, were prepared by reverse phase evaporation method. Two types of interaction between liposomes and chitosan were investigated: chitosan addition into lipidic bilayer during liposome preparation and coating of already formed liposomes with chitosan. Glycolic acid loaded chitosan microspheres were prepared by the dry-in-oil emulsion method. The microparticulate systems were morphologically characterized by electron microscopy and particle size analysis. In vitro dissolution tests were performed to evaluate the feasibility of microparticulate systems in modulating glycolic acid release. The results obtained show that liposomes are always suitable to modulate glycolic acid release and that the best condition to achieve this control is obtained by the liposomal systems in which glycolic acid/lipid molar ratio is 5:1. Further significant release control is obtained by addition of chitosan into the liposomes, while chitosan microspheres are not able to control glycolic acid release even after crosslinking.

Evaluation of spray drying as a method for polylactide and polylactide-co-glycolide microsphere preparation

Polylactide and polylactide-co-glycolide microspheres containing a lipophilic model drug (vitamin D3) were prepared by spray drying. The purpose of this work is to evaluate the efficacy of spray drying as a method for microsphere preparation. The study was carried out on five different polymers of lactide class: poly-L-lactide 57000 MW, poly-D,L-lactide 209,000 MW, 109,000 MW, 16,000 MW, and polylactide-co-glycolide 22,000 MW. The process conditions were experimentally assessed for each polymer used. The microspheres obtained were characterized for their shape, size and drug content, and the influence of the polymer on microsphere characteristics was evaluated. Results show that polymer type, polymer molecular weight and its concentration in the spraying solution greatly affect microsphere characteristics. In vitro dissolution tests performed with the rotating bottle method resulted in different release profiles depending on type of polymer and on microsphere morphology.

Gamma irradiation effects on stability of poly(lactide-co-glycolide) microspheres containing clonazepam.

This work was aimed at evaluating the effects of gamma irradiation on the stability of microspheres made of a poly(lactide-co-glycolide) copolymer (PLGA) and loaded with 15% w/w of clonazepam (CLO). The influence of CLO on PLGA radiolysis mechanisms and the identification of possible irradiation markers were also investigated. Microspheres were prepared by means of a spray-drying method. gamma Irradiation was carried out either under vacuum or in air, at a dose of 25 kGy, by using a 60Co source. The stability of CLO loaded microspheres was evaluated over a 6-month period on the basis of drug content and dissolution profile. Radiolysis mechanisms were investigated by using electronic paramagnetic resonance (EPR) analysis. The microspheres irradiated under vacuum were stable over the considered period of time. After irradiation in air, CLO release rate increased by approximately 10%, and did not change further in the following period of storage. The EPR analysis showed some radicals arising from both the polymeric matrix and the active ingredient. Polymer/CLO spin transfer reactions suggest that CLO had a radio-stabilising effect on the polymeric matrix. In the loaded microspheres, the intensity in time of the CLO radical signal is sufficient for its possible use as irradiation marker.

Solvent evaporation, solvent extraction and spray drying for polylactide microsphere preparation

Abstract Polylactide microspheres containing vitamin D 3 (D 3 ) as a model drug were prepared by solvent evaporation, solvent extraction and spray drying. In this work, these three different preparation methods were compared and the extent to which each can affect the properties and characteristics of microspheres was identified. The experimental conditions yielding the best results were chosen within each method. Solvent extraction proved to be the better of the two traditional methods. It resulted in particles that were more regular in shape, smaller, with a narrower size distribution and higher porosity. Spray drying yields results equivalent to those of solvent extraction with the advantage of a higher encapsulation efficiency and shorter duration for the process of preparation. Moreover, the dissolution profile of microspheres prepared by spray drying demonstrated that more gradual release of drug was promoted.

A multiple emulsion method to entrap a lipophilic compound into chitosan microspheres

A new method for preparation of chitosan microspheres loaded with an hydrophobic drug, ketoprofen, was developed. It is an emulsification/solvent evaporation process carried out in mild conditions and particularly useful for microencapsulation of thermally sensitive drugs. This method can be additionally combined to physical and chemical cross-linking in order to modulate drug release. Physical cross-linking was carried out by dry heating chitosan microspheres at fixed temperatures and for different times. Glutaraldehyde at different concentrations was used as the chemical cross-linking agent on microspheres constituted by different theoretical ketoprofen/chitosan ratio (1:2, 1:4, 1:6 w/w). Chitosan microspheres were morphologically characterized for shape, surface characteristics and size distribution; chitosan/ketoprofen interactions inside microspheres were investigated by differential scanning calorimetry and powder X-ray difractometry. Ketoprofen contents inside the microspheres and in vitro drug release profiles were also determined.