Preparation Process and in vitro release performances of HPMC-coated systems for pulsatile release of verapamil

The aim of this work was to evaluate the preparation process and in vitro release performances of HPMC coated systems for pulsatile release, containing verapamil as the active ingredient. Tableted cores of different size, formulated either for an immediate or prolonged drug liberation, were investigated in order to possibly meet diverse needs connected with the chronotherapy of ischemic heart disease, mainly occurring around awakening time.Tablets containing different amounts of verapamil hydrochloride were obtained by rotary press (AM8S, Ronchi, I) and coated with HPMC (Methocel\uaeE50 8% w/v aqueous solutions) in a tangential-spray rotary fluid bed (GPCG 1.1 Glatt\uae, D) equipped with a Teflon-coated disk. Release tests (n=3) were performed in a three-position USP28 disintegration apparatus (DT3, Sotax, CH; 800 ml distilled water, 37.0\ub10.5\ub0C). A single test unit was placed in each basket-rack assembly. Fluid samples were withdrawn automatically at fixed time points. Acetaminophen was quantified by spectrophotometer.The selected operating conditions allowed a feasible, high-yield process to be performed on the tablets in exam. Moreover, thanks to the relative flexibility of the coating technique, only minor modifications were introduced when coating different size cores. The in vitro release tests carried out on immediate release tablets with increasing coat thickness showed a typical lag phase preceding the prompt release of verapamil. Delayed release performances dependent on the coating level were also exhibited by systems prepared starting from prolonged release cores. From such systems, as pursued, the drug was released slowly over an extended time period. For all system typologies, a linear relationship was found between lag time and the applied amount of coating polymer.The results obtained in terms of low-viscosity HPMC-based aqueous spray-coating feasibility and programmable delayed release behavior seem to point out a potential suitability of the system for evening-dosing chronotherapy of ischemic heart diseas

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

Oral chronotopic\uae drug delivery systems: Achievement of time and/or site specificity

A delayed release system, based on the coating of cores with hydrophilic derivatives of cellulose (hydroxypropylmethylcellulose) and useful for controlling time and/or site of delivery, is described. The overall mechanism responsible for the burst in release profile after a predetermined lag- phase, based on the water/polymer interaction, is outlined. In vitro release data from systems prepared by press-coating or spray-coating of fast disintegrating cores containing model drugs (indomethacin or verapamil \ub7 HCl) are reported

Thermal properties and mechanical stress of \u3b2-cyclodextrin

A comprehensive picture of the thermal behaviour of \u3b2-cyclodextrin was obtained from experiments involving differential scanning calorimetry (DSC), thermogravimetry (TG), thermomechanical analysis (TMA), and hot stage microscopy (HSM). X-ray powder diffractometry (XRD) was used as a complementary technique to detect solid-solid phase transitions of \u3b2- cyclodextrin. Untreated and handled (recrystallized from water, ground, or compacted) samples of commercial \u3b2-cyclodextrin showed different thermodynamic and thermomechanical properties. This should be taken into account when \u3b2-cyclodextrin is used as a pharmaceutical excipient, particularly in tablet technology, since the physical state and the bulk properties of the powder material may be one of the important factors influencing the characteristics of the dosage form

Time-controlled oral delivery systems for colon targeting

A review. In recent years, many research efforts have been spent in the achievement of selective delivery of drugs into the colon following oral administration. Indeed, colonic release is regarded as a beneficial approach to the pharmacol. treatment or prevention of widespread large bowel pathologies, such as inflammatory bowel disease and adenocarcinoma. In addn., it is extensively explored as a potential means of enhancing the oral bioavailability of peptides, proteins and other biotechnol. mols., which are known to be less prone to enzymic degrdn. in the large, rather than in the small, intestine. Based on these premises, several formulation strategies have been attempted in pursuit of colonic release, chiefly including microflora-, pH-, pressure- and time-dependent delivery technologies. In particular, this review is focused on the main design features and release performances of time-controlled devices, which rely on the relative constancy that is obsd. in the small intestinal transit time of dosage form

Oral pulsatile drug delivery systems

In the field of modified release, there has been a growing interest in pulsatile delivery, which generally refers to the liberation of drugs following a programmable lag phase from the time of administration. In particular, the recent literature reports on a variety of pulsatile release systems intended for the oral route, which have been recognized as potentially beneficial to the chronotherapy of widespread diseases, such as bronchial asthma or angina pectoris, with mainly night or early morning symptoms. In addn., time-dependent colon delivery may also represent an appealing related application. The delayed liberation of orally administered drugs has been achieved through a range of formulation approaches, including single- or multiple-unit systems provided with release-controlling coatings, capsular devices and osmotic pumps. Based on these premises, the aim of this review is to outline the rational and prominent design strategies behind oral pulsatile delivery

Erodible perforated coated matrix for extended release of drugs

A new oral modified release system exibiting an in vitro constant release rate has been designed and prepared. The system consists of an erodible matrix core with a central hole and is partially covered with an impermeable polymeric film. The perforated core is made of a low viscosity hydroxypropylmethylcellulose (HPMC); metoprolol tartrate and benfluorex were used as model drugs. The inner hole surface is the only releasing surface of the system. This system can be prepared by using both conventional tabletting and film coating processes

Oral pulsatile delivery systems based on swellable hydrophilic polymers

Upon contact with aqueous fluids, swellable hydrophilic polymers undergo typical chain relaxation phenomena that coincide with a glassy-rubbery transition. In the rubbery phase, these polymers may be subject to swelling, dissolution and erosion processes or, alternatively, form an enduring gel barrier when cross-linked networks (hydrogels) are dealt with. Because of the peculiar hydration and biocompatibility properties, such materials are widely exploited in the pharmaceutical field, particularly as far as hydrophilic cellulose derivatives are concerned. In oral delivery, they have for long been employed in the manufacturing of prolonged release matrices and, more recently, for pulsatile (delayed) release devices as well. Pulsatile delivery, which is meant as the liberation of drugs following programmed lag phases, has drawn increasing interest especially in view of emerging chronotherapeutic approaches. In pursuit of pulsatile release, various design strategies have been proposed, chiefly including reservoir, capsular and osmotic formulations. In most cases, water-swellable polymers play a key role in the overall delivery mechanism after being activated by physiological media. Based on these premises, the aim of the present review is to survey the main oral pulsatile delivery systems, for which swelling, dissolution and/or erosion of hydrophilic polymers are primarily involved in the control of release