M.J. Lucero

A study of shear and compression deformations on hydrophilic gels of tretinoin

Abstract A rheological study of hydrophilic gels of Carbomer® 940 with tretinoin as the drug, and ascorbic acid as an antioxidant, has been carried out. At the same time, the effect of storage time has been determined. Both shear and compression deformations were applied. From the results obtained, correlations between both types of deformation have been established. The results were statistically significant between shear and compression stresses, and between shear stress and area of spreading.

Determination and pharmacokinetic profile of liposomal foscarnet in rabbit ocular tissues after intravitreal administration.

The treatment of ocular diseases affecting the posterior segment of the eye, such as cytomegalovirus (CMV) retinitis, requires the access of the drugs to the vitreous humor. Foscarnet inhibits replication of herpesviruses, including CMV. The drugs encapsulation in liposomes is meant not only to increase activity and to prolong the effect of the drug, but also to reduce its toxicity. The aims of the present study were to evaluate foscarnet levels and its pharmacokinetic parameters in vitreous humor and retinal tissue of rabbits after the administration of an intravitreal injection of both liposomal foscarnet and foscarnet commercial solution. Liposomes were prepared by the reverse-phase evaporation method. The amount of encapsulated foscarnet (F) was 63% wt. The in vitro diffusion assays showed that F was released more slowly when formulated in liposomes than in the commercial solution. The in vivo studies showed that, as opposed to commercial solution F, liposomal F achieves stable and durable therapeutic levels in retina, going beyond 72h, reaching the vitreous humor with adequate levels to accomplish the aims of intravitreal therapy. Lyophilization also increased stability and dispersion of liposomes in aqueous medium, although not improving the pharmacokinetic results over those from non-lyophilized liposomes.

Stability of hydrophilic gels of tretinoin

Tretinoin is the trans isomeric form of retinoic acid. Its chemical structure includes a functional acid group and a side chain with conjugated double bonds, both susceptible to redox reactions. The vitamin C redox system comprises l-ascorbic acid, monodehydroascorbic acid and dehydroascorbic acid. Each of these substances has different physicochemical properties but possess antioxidant capacity for both hydrophilic and lipophilic substances. The present work is centred on studying the stability of hydrophilic gels of tretinoin prepared with or without antioxidant. HPLC was used to validate the analytical and extraction techniques to determine the amounts of tretinoin remaining. The results indicate that tretinoin undergoes rapid degradation by oxidation of the conjugated double bonds which is neither retarded nor lessened by the presence of antioxidant.

A rheological study of semisolid preparations of Eudragit

Abstract The present work studies the rheology of semisolid preparations of acrylic polymers of Eudragit

Novel aqueous chitosan-based dispersions as efficient drug delivery systems for topical use. Rheological, textural and release studies.

The use of a novel cross-linked thiolated chitosan (CTS) was investigated as the main component of aqueous dispersions (at 1% and 3% w/v) for topical drug delivery systems. The nonionic theophiline (Th) and the cationic diltiazem(.)HCl (Dt) (at 0.5% w/v concentration) were used as model drugs. All aqueous dispersions behaved as viscoelastic fluids. The CTS 1% dispersions showed predominance of viscous component and low viscosity. However, in the CTS 3% dispersions, both the elastic component and high viscosities prevailed. So, texture parameters improved from CTS 1% to 3% dispersions and CTS 3%-Dt showed greater cohesion and adhesion than CTS 3%-Th, but always below CTS alone. All dispersions showed a Fickian diffusion mechanism. Despite release profiles of both drugs almost fully overlapped at 1% CTS, diffusion coefficients confirmed Dt released faster than Th at 3% CTS. The rheological behavior and the chemical nature of the drugs explained these results.

Therapeutic efficacy of hydrophilic gels of α-tocopherol and tretinoin in skin ulcers induced by adriamycin hydrochloride

Abstract α-Tocopherol, tretinoin and ascorbic acid can act as biological antioxidants. Hydrophilic gels of these drugs were prepared, alone or in combination, and their therapeutic efficacy on ulcers induced by adriamycin hydrochloride in experimental animals was studied. The qualitative study considered the four phases observed and clearly defined: ulcer, scab, crater and cicatrix. The quantitative study yielded results showing statistically significant differences between the animals treated with tretinoin and those receiving α-tocopherol. Tretinoin was not shown to be effective in reducing either the size of the lesion or the time of disappearance of the acute period with respect to control; moreover, the ulcers were even larger than those of control. α-Tocopherol administered in semisolid vehicles protects the epidermal cells from free radical attack, as indicated by the reduction in lesions induced by the promoter (adriamycin hydrochloride). At the same time it may accelerate epidermal regeneration. This double activity — protection and regeneration — is potentiated by the presence of ascorbic acid in the formulations, as shown by the smaller size of the ulcers and the shorter duration of the acute effects.

A study of shear and compression deformations on hydrophilic gels of α-tocopherol

Abstract A rheological study of hydrophilic gels of Carbomer ® 940 with α-tocopherol as drug, and ascorbic acid as antioxidant, has been carried out. At the same time, the effect of storage time has been determined. Both shear and compression deformations were applied. From the results obtained, correlations between both types of deformation have been established. The results were statistically significant between shear and compression stresses, and between shear stress and area of spreading.

Protection by α-tocopherol against skin ulcers induced by ionizing radiations

Abstract An in vivo study was carried out to determine the protective character of α-tocopherol against lesions caused by free radicals of ionizing radiation. Emulsified vehicles (o/w) were used at dosages of 1.5 and 2.5% w/w of α-tocopherol. To promote generation of free radicals, we used 6 MeV electrons from a lineal accelerator; a dosage of 2800 cGy was selected. The lesions were assessed according to the indications of the WHO, modified for such an effect. Biopsies of the treated areas were taken at the moment of maximum acute toxicity in order to subject them to an anatomopathological study, evaluating five parameters: thickness of epidermis, squamous metaplasia of the adnexa, overall impression, follicular atrophy and density of fibroblasts. The conclusions of this study indicate that under the experimental conditions used, α-tocopherol, applied topically, protects the skin from ionizing radiation, giving rise to a thicker epidermis than found in healthy animals.

Physicochemical stability of a new topical timolol 0.5% gel formulation for the treatment of infant hemangioma

Abstract Infant hemangioma (IH) is the most common tumor in infants, which affects 5–10% of white children. It is a tumor of vascular origin that appears in the first months of life. The indication for the treatment of the IH is not approved in the datasheet of the product, however it has been used in the infant hemangioma by topical administration as an alternative to oral propranolol, avoiding the main problems of the oral route (bradycardia and hypotension). The objective of this work is to study the physical and chemical (HPLC stability indicating method) stability of a 0.5% timolol gel for topical application during 60 days (considering the stability limit as 90% of initial concentration of timolol maleate). The gel was prepared with a polyacrylic acid derivative and the physical stability of the system was studied by visual control, rheological and mechanical characterization. The studied formulation guarantees the correct dose administering and stability after 60 days stored at 25 ± 2 °C and light protected (tube of aluminum). We have developed an easy topical gel for the treatment of infant hemangioma with physical and chemical stability higher than those provided by the majority of hospitals.

Physicochemical stability of captopril and enalapril extemporaneous formulations for pediatric patients

Abstract The prevalence of hypertension among children has been increasing. Community and Hospital Pharmacists are often challenged to provide an oral liquid extemporaneous formulation for pediatric patients, because there are no appropriate dosage drugs to the specific needs of the child. The objective of this study is to choose and develop suitable pediatric extemporaneous formulations for captopril and enalapril maleate and to determine their physicochemical stability. A survey was carried out to evaluate the extent of dispensation of these drugs in Hospitals in Spain. Stability studies of formulations have been studied according to ICH normative at 5, 25 and 40 °C. Three samples from each temperature were withdrawn and assessed for stability on days 0, 15, 30, 50 and 90 using a high-performance liquid chromatography (HPLC) mass spectrometer assay. Rheological studies were carried out to ensure the maintenance of the physical characteristics of these non-Newtonian fluids. Captopril and enalapril maleate formulations used the pure drug and were stable during 50 days at 5 °C. We have developed easy antihypertensive oral liquid extemporaneous formulations for pediatric patients with physical and chemical stability higher than those provided by the majority of Hospitals.