Lorena Muggetti

Technological induction of mucoadhesive properties on waxy starches by grinding

Abstract In the present work the mucoadhesive properties of two native starches (maize starch and waxy maize starch) and one pregelatinized waxy maize starch have been investigated. Subsequently the possibility of inducing or improving the mucoadhesive properties of these starches by simple technological processes such as milling and spray-drying has been assessed. Native starches were first checked for physical properties [intrinsic viscosity, thermal behaviour (differential scanning calorimetry, DSC) and solubilization index] and compared with the pregelatinized starch. The mucoadhesive properties of the starches were evaluated by means of two in vitro methods: rheological analysis and tensile stress testing. Both native and pregelatinized starches were subsequently subjected to milling and spray-drying. The technological variables analyzed were the type of mill (from laboratory to pilot-plant scale) and the process conditions (milling time and cooling temperature of the grinding chamber). The results show that mucoadhesive properties can be induced in waxy maize starch by grinding or milling, i.e., by very simple and cheap technological processes. These processes are efficient only when effected in high-energy mills. Whereas the increase in milling time was shown to improve the mucoadhesive properties of the final products, the cooling temperature of the grinding chamber had no detectable influence. Spray-drying as itself is not capable of inducing mucoadhesive properties on native starches and does not improve the mucoadhesive properties of milled waxy starch and pregelatinized starch. DSC analysis indicated that, at least for the materials considered, gelatinization, either obtained by cooking and subsequent spray-drying (as for pregelatinized starch) or by simple grinding (as for waxy starch), is a necessary requisite to induce mucoadhesive properties.

Critical micellar concentration shifting as a simple tool for evaluating cyclodextrin/enhancer interactions

Abstract It has previously been found that the undesirable side effects of enhancers may be reduced, virtually without affecting their promoting absorption actions, when they are used in combination with a cyclodextrin. Many enhancers are amphiphilic moieties able to form micelles in solution. The enhancing effect is ascribed to the free molecules in solution. Their toxic effects seem to be linked to the solubilization of cell membrane components (Such as phospholipids or cholesterol), due to micelles formed by the enhancers. A study on the influences of cyclodextrins on critical micellar concentration (cmc) shifting has been carried out by surface tension measurements. The formation of a complex in solution between the cyclodextrin and the enhancer shifts cmc to higher values, and changes the ratio between free and micellized molecules of the enhancer, thus minimizing its toxic effects. Laureth-9, quaternary ammonium salts and cholic acid derivatives were considered as enhancers. Changes in buffering salts and tonicity of the measuring medium were also taken into consideration as formulative variables.

Stability studies on a steroidal drug/β-cyclodextrin coground mixture

Abstract The aim of this study was to investigate the physico-chemical changes and the chemical stability of a steroidal drug, 6-methylenandrosta-1,4-diene-3,17-dione (FCE24304), an aromatase inhibitor, in the presence of β-cyclodextrins (β-cd) using a cogrinding procedure which enables amorphization. Results of stressed conditions stability tests are shown, with particular regard to the presence of moisture, and evaluated by HPLC, DSC and X-ray diffractometry techniques and correlated with the dissolution rate behavior. The transformation of the amorphous drug/β-cd system into a 1: 2 mol/mol crystalline complex is indicated.

Stability studies on steroidal drug/β-cyclodextrin kneaded systems

Abstract 6-Methylenandrosta-1,4-diene-3,17-dione (FCE24304), an aromatase inhibitor, is characterised not only by poor solubility in aqueous media and slow dissolution rate, but also by low chemical stability due to possessing conjugate double bonds. Several approaches have already been evaluated for improving both the biopharmaceutical properties and chemical stability of drugs in a particular way by the use of β-cyclodextrin. An accelerated short-term stability study on FCE24304β-cyclodextrin kneaded systems, prepared using two different molar ratios, was carried out and the systems evaluated by HPLC, DSC and X-ray difiractometry techniques and correlated with dissolution rate behaviour. A tablet formulation with a 1:2 molar ratio of the FCE24304/β-cyclodextrin complex is now under development.

Use of Dehydrated Beta-Cyclodextrin as Pharmaceutical Excipient

Cyclodextrins, and expecially beta ones, are widely used in the pharmaceutical field for their ability of improving the solubility and the stability of drugs by complex formation at the solid state. Such phenomenon occurs only when cyclodextrin has a certain water content, being the removal of water from internal cavity essential for the interaction between the drug and the excipient. Anyway, the dehydration of beta cyclodextrin leads to a product with peculiar properties, which is reported to be not able to form inclusion complex at the solid state, but is very effective in increasing the rate of complex formation in solution with a consequent strong influence on dissolution performances of drugs. This approach is extremely interesting for obtaining fast dissolving tablets of drugs that are able for their own characteristics, to form stable solid inclusion complexes only in solution, but not at the solid state. The formulation process is extremely simple and of low cost involving only the physical mixing...

Preformulation activities of intranasal dosage forms of temazepam

Abstract Bioadhesive excipients are used in intranasal drug delivery to prolong the residence time of formulations at the absorption site with the aim of improving the biopharmaceutical properties of the active drug. Bioadhesive starch, obtained by a high energy grinding process starting from a waxy starch (that does not possess any bioadhesive properties), has been employed to prepare different intranasal temazepam-starch formulations. Physico-chemical characterization of these formulations has been performed by means of theological, thermal, chromatographic and particle size distribution tests both after the preparation processes and during a 6-month storage period in different temperature and relative humidity conditions. All formulations revealed good bioadhesive properties after the manufacturing processes and a good chemical and physico-chemical stability during aging.

Nasal and pulmonary drug delivery systems

The respiratory route of administration has long been the medically desired drug delivery portal for the administration of topical anti-inflammatory drugs. These drugs are administered either to the lung, i.e., the lower respiratory system to treat asthma, or to the nasal cavity, i.e., the upper respiratory system to treat allergic rhinitis. This therapeutic focus dominates the drug delivery applications for the respiratory system. More recently, the respiratory system has provided a non-invasive method for the administration of biotherapeutics. And finally, formulation and device advancements have led to the consideration of the respiratory route for a number of other therapeutic applications where systemic delivery is desirable. All of these factors have resulted in the therapeutic patents that are discussed in this review.