Gaetano Bignardi

Development and Characterization of a Buccoadhesive Dosage Form of Oxycodone Hydrochloride

AbstractA buccoadhesive system for the delivery of oxycodone hydrochloride to the oral mucosa was prepared from a colloidal solution of gelatin used as a bioadhesive agent. An in vitro method for measuring the adhesion of release system to a substrate was developed by employing a modified balance. The eflects of thickness and of the presence of the drug on swelling and mucoadhesion properties were evaluated. The in vitro release of the buccoadhesive formulation was studied by a USP paddle dissolution apparatus and the results were fitted to an empirical equation. In vivo compliance and permanence time in 10 healthy volunteers were estimated.

An example of application of a mixture design with constraints to a pharmaceutical formulation

The aim of this tutorial is to show the application of a mixture experimental design to a problem of pharmaceutical formulation. A gel, based on poloxamer 407, useful for topical administration of tolfenamic acid, a potent anti-inflammatory drug very poorly soluble in water, has been prepared, and a mixture experimental design was used to study the influence of the components on the viscosity of the formulation. Its application allowed to identify a critical boundary, separating semisolid formulations from liquid ones, within a narrow interval of concentrations of the components, and to estimate their effects on the viscosity of the preparation.

Development and In Vitro Evaluation of Buccoadhesive Tablets Using a New Model Substrate for Bioadhesion Measures: The Eggshell Membrane

For oral delivery of antimicrobial and anti-inflammatory drug, mucoadhesive tablets based on gelatin/hydroxypropylcellulose (HPC), gelatin/hydroxypropylmethyl-cellulose (HPMC), and gelatin/sodium carboxymethylcellulose (NaCMC) at different ratios were prepared by direct compression of the mixed powders. Metronidazole and benzydamine were used as model drugs. The in vitro bioadhesive properties, evaluated by a commercial tensile tester, were significantly affected by the model substrate employed, that is, a polypropylene (PP) membrane or a biological membrane (eggshell membrane). The use of the biological substrate seemed to supply more reliable data. All studied formulations showed an erosion-diffusion mechanism of release, anomalous or non-Fickian release, in agreement with the behavior of the swellable systems.

Stability indicating HPLC assay for retinoic acid in hard gelatine capsules containing lactose and as bulk drug substance

A reversed phase high performance liquid chromatographic assay for determination of Retinoic Acid in raw materials and in hard gelatine capsules containing Tablettose® as excipient is described. The method uses a UV diode array detector. The solution concentrations were measured on weight basis to avoid the use of an internal standard, otherwise necessary for the presence of the undissolved matrix. The study of the recoveries, planned in a Latin square as experimental design, shows that the accuracy and precision of the method are excellent. The assay is selective and stability indicating. The method resolves three related substances (13-cisretinoic acid, 5,6-epoxy-5,6-dihydroretinoic acid and 4-oxo-retinoic acid) with quantitation in the range 0.04 % 0.2 % of the labelled amount of Retinoic Acid (10 mg).

Development, characterization and preliminary clinical evaluation of mucoadhesive vaginal gels containing chlorhexidine digluconate

Gels containing chlorhexidine, based on hydroxyethylcellulose or its mixtures with either hydroxypropylmethylcellulose or chitosan, were prepared and characterized by in vitro drug release, swelling, mucoadhesion and rheological studies. All formulations provided a controlled drug delivery showing in general a decrease in drug release rate with the increase of the total polymer concentration. Formulations containing either hydroxyethylcellulose or its mixtures with hydroxypropylmethylcellulose presented similar strength of gel network that was markedly higher compared to gels based on mixtures with chitosan at the same total polymer concentration. Drug release was more sustained when gel components were mixtures of hydroxyethylcellulose and hydroxypropylmethylcellulose. Mucoadhesion was similar for all preparations. Viscosity measurements gave higher values in correspondence to higher total polymer concentrations. A candidate vaginal gel formulation containing hydroxyethylcellulose at 2.5% (w/w) induced a clinical remission in 93% of patients affected by bacterial vaginosis compared to 76% of patients belonging to a metronidazole treatment group, and in 84% of subjects with Candida infections compared to 83% receiving clotrimazole. No adverse events were reported during the trial in any patient. Patient compliance with the mucoadhesive gel was good.

Stability Study of Hard Gelatin Capsules Containing Retinoic Acid

Retinoic acid (RA) is employed in the therapeutic treatment of acute promyelocytic leukemia (APL). In this paper, the chemical stability and the most favorable storage conditions of RA in hard gelatin capsules containing α-lactose monohydrate, used in clinical experimentation, are reported. A secondary goal of this work was to show the usefulness of a robust regression technique, repeated median with replicates (RMWR) in a solid-state shelf life prediction by accelerated studies. The capsules were stored at room temperature and in the freezer. Their residual RA content was assayed for more than 3 years. RA chemical degradation was monitored by high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) stability-indicating methods previously validated and able to detect various potential degradation products. Possible physical modifications were checked by dissolution tests and differential scanning calorimetry (DSC) of the content of the capsules. The shelf life was also predicted by an accelerated isothermal method to confirm room temperature results, and the activation energy estimated through this study was 12.5 ± 1.1 kcal/mol (95% confidence interval). In the conditions of climatic zone II, the shelf life for the capsules stored at room temperature in light-resistant containers was equal to 678 days, while the capsules stored in the freezer retained the initial content of drug after 1289 days. From the results gathered in this study, the usefulness of RMWR for shelf life prediction in the presence of outliers is evident.

Study of the Interaction of Dithranol with Heptakis(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin in Solution and in the Solid State

The interaction between dithranol and heptakis(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin (TMBCyD) has been investigated in aqueous solution containing isoascorbic acid (0·2% w/v) as antioxidant and in the solid state. The interaction in the solid state was studied by differential scanning calorimetry (DSC), infrared spectroscopy (IR), X‐ray powder diffractometry (XPD) and a dissolution‐rate method.