Jamila Hamdani

Physical and thermal characterisation of Precirol and Compritol as lipophilic glycerides used for the preparation of controlled-release matrix pellets.

Physical and thermal properties of Compritol and Precirol as potential lipophilic binders in melt pelletisation process for the preparation of sustained-release matrix pellets were evaluated in this study. Experimental measurements were carried out using X-ray diffractometry, differential scanning calorimetry (DSC), hot-stage microscopy (HSM) and rheological measurements. These studies have shown that the lipophilic binders may present a relatively complex behaviour depending on the sample treatment (untreated, freshly solidified, aged samples). DSC and HSM methods have shown the presence of polymorphism for Precirol. Moreover, both untreated and fresh solidified Precirol and Compritol samples present partially amorphous layered structure which slowly crystallise in time. The rate of crystallisation was found to be more rapid for Precirol, and highly dependent on the ageing conditions (storage temperature). Finally, the evaluation of the thermal and rheological properties of Precirol and Compritol mixtures have shown that the use of such mixtures, presenting well distinct melting properties, could be a very interesting tool for the preparation of high fatty binder content prolonged-release pellets in high shear mixers if the product temperature is carefully controlled (between 45 and 50 degrees C) during the pelletisation process.

Development and evaluation of prolonged release pellets obtained by the melt pelletization process

This study was performed in order to evaluate the possibility of obtaining prolonged release matrix pellets by a melt pelletization process in a laboratory high shear mixer (Mi-Pro, Pro-C-epT). Phenylephrine hydrochloride pellet formulations based on lactose 450 mesh and a mixture of Compritol 888 and Precirol ATO 5 as melting binders were evaluated. The fatty binder content of pellets was substantially increased (from 18 to 80% w/w). The effects of jacket temperature, massing time (MT) and impeller speed (IS) on the pellet characteristics were investigated. It was shown that pellets of narrow size distribution can be produced by using an IS of 800 rpm, a chopper speed of 4000 rpm and a MT of 8 min. On the other hand, the applicability of this technique for the production of sustained-release pellets using ciprofloxacin hydrochloride, ketoprofen and theophylline as less water soluble model drugs than phenylephrine hydrochloride was also studied. This study demonstrated that formulations based on an appropriate mixture of Precirol and Compritol can be used to produce in a short time prolonged release pellets for very hydrosoluble drugs like phenylephrine hydrochloride as well as for the other drugs tested.

In vitro and in vivo evaluation in healthy human volunteers of floating riboflavin minitablets

This work relates to sustained-release floating minitablets which are able to float on the surface of aqueous fluids for an extended period of time. Firstly, granules were prepared by melt granulation and then, compressed into minitablets to obtain a multiple-unit system. Formulations were based on the use of a meltable binder, a swellable hydrocolloid and on a mixture of gas-generating agents. In vitro and in vivo evaluations of floating capability were performed. To assess the usefulness of the intragastric buoyancy properties of the floating minitablets (FMT), non-floating minitablets (NFMT) with in vitro riboflavin (RF) release profiles equivalent to the FMT were prepared. FMT and NFMT were administered orally to nine healthy volunteers. The volunteers were divided into two groups, a fasted group (n = 5) and a fed group (n = 4). The pharmacokinetic parameters were investigated by analysis of riboflavin urinary excretion leading to the observation that the mean amount of riboflavin excreted in the urine seemed to increase when FMT were administered after a meal, but did not increase when NFMT were administered. As riboflavin has a narrow absorption window in the upper part of small intestine, this phenomenon could be attributed to gastric retention of the floating minitablets.

Evaluation of compliance with isotretinoin PPP recommendations and exploration of reasons for non-compliance: Survey among French-speaking health care professionals and patients in Belgium

To evaluate awareness of and compliance in Belgium by French‐speaking health care professionals and patients with the isotretinoin safety recommendations regarding its teratogenic risk.