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Abstract The preparation of sustained release dosage forms of Carbamazepine (anti-epileptic drug characterized by a very low water solubility and by a short half life on chronique dosing) was carried out. These formulations were obtained in two different steps: a) modified release granules were prepared by the loading of cross-linked sodium carboxy...

Abstract Drug constant release is not always the desired solution for controlled drug administration; some therapeutic situations require consecutive pulses of active principle A biphasic oral delivery system able to release an immediate dose of therapeutic agent as well as a further pulse of drug after some hours could be interesting In order to o...

Abstract The development of a disintegrating force inside the tablet due to the liquid/solid contact depends on a proper wetting of the material and occur according to saturation kinetics. The aim of the present work is the evaluation of such a force development in relation to the characteristics of the tablet in particular to the compression force...

Water penetration and disintegrating force measurements were combined with the aim of assessing the role played by various mechanisms in the disintegration process. Nine tablet series, made of differing base materials (α-lactose monohydrate, dicalcium phosphate dihydrate and acetylsalicylic acid) such as are likely to elicit differing disintegratio...

Controlled release pharmaceutical compositions administrable by oral route, containing as the active principle at least one salt of the gamma hydroxy butyric acid with a pharmaceutically acceptable cation, for the treatment of alcoholism, opium like substances addiction, heroin addiction, food and nicotine addiction, depressive and anxious states,...

The preparation of hydrophilic matrix tablets able to release naftazone, a water-insoluble drug, into an aqueous medium at a constant rate (zero-order dissolution) is described. Enhancement of dissolution rate of the drug was achieved using cross-linked carmellose sodium, beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin. Hypromellose was used a...

A new multi-layer tablet device is proposed for the extended release of drugs at a constant rate. It consists of the application, during tabletting, of compressed barrier layers on one or both surfaces of a hydrophilic matrix containing the active ingredient. The barriers can limit the core hydration process by maintaining the planar surfaces of th...

A new dry-coated device for the release of drug after a programmable period of time is proposed. It is intended to be used mainly in the therapy of those diseases which depend on circadian rhythms. Some core formulations, characterized by different release rates and mechanisms (containing diltiazem hydrochloride or sodium diclofenac as model drugs)...

In recent years many attempts have been made to modify drug release profiles from hydrophilic matrix tablets. Recently a new method based on the application of an inert impermeable coating on different sides of a matrix tablet was proposed. The coating delays the interaction of the matrix with the dissolution medium. In this way the hydration rate...

The preparation and in vitro characterization of extended release erodible hydrophilic matrices containing a water insoluble drug (carbamazepine) are described. The matrices are obtained by tabletting mixtures of the drug with a water swellable polymer (cross-linked sodium carboxymethylcellulose) and a water gelling polymer (hydroxypropylmethylcell...

Hydroxypropyl β-cyclodextrin (water-soluble cyclodextrin) is proposed as a constituent of extended-release dosage forms (erodible hydrophilic matrices made of hydroxypropylmethylcellulose) which are able to release a water-insoluble drug (diazepam) at a fairly constant rate, until almost the entire drug content is released from them. Hydroxypropyl-...

The realization of programmable constant release oral dosage forms designed for the extended release of a water-insoluble benzodiazepine (diazepam), is described. The dosage forms are constituted by hydrophilic matrix tablets which are obtained by direct compression of the drug with two different kinds of cellulose ethers: a water swellable polymer...

After oral administration of basic drugs, the different pH values of the gastrointestinal tract can result in drastic changes in drug solubility, which can be very high at acidic pH values and dramatically low at neutral/basic pH, with consequent problems for the design of oral extended release formulations. In this paper, the preparation of an ora...

Polymeric barriers applied by compression have already been used to control drug release rate from matrix tablets. In this paper, polymeric barrier layers, used to prepare and develop a new device able to release the drug after a programmable period of time, are described. Some matrix core formulations, containing Trapidil or Sodium Diclofenac as a...

Prolonged medication with diltiazem has proved advantageous in the treatment of coronary insufficiency and arterial hypertension. Consistently, a number of extended release formulations, based on different retardation mechanisms, have been proposed. In the present work two prolonged release oral formulations containing diltiazem, one intended for t...

Three industrial batches of a 10% (w/v) amino acid solution have been checked for particulate contamination. The batches differed in preparative technology and/or type of additives. In particular, one batch was prepared under nitrogen, filled under vacuum and with the addition of sodium metabisulfite and cysteine. The other two batches were simply...

Swellable matrix systems with anomalous release kinetics are suitable solutions for drug release control for oral administration. Generally, the release rate modulation is achieved through the use of different types of polymer or the employment of soluble or insoluble fillers. The resulting release mechanism depends on the relative importance of ta...

The application of differential scanning calorimetry (DSC) is described for investigating the interaction between trimethoprim and sulfamethoxypyridazine in suppository formulations containing fat bases (Suppocire, Novata, Witepsol). The thermal behavior of suppositories at various storage times is deeply influenced by the fat base and by interacti...

A superdisintegrant (cross-linked sodium carboxymethylcellulose, Ac-Di-Sol was used for the enhancement of the dissolution rate of carbamazepine, an anti-epileptic drug characterized by very low water solubility. Three different drug/polymer systems were prepared: a physical mixture and two loaded systems obtained using a solvent evaporation method...

The dissolution rate is often the limiting step in gastrointestinal absorption of water insoluble drugs from solid oral dosage forms. The aim of this work was to use a swellable polymer chosen among superdisintegrants, for improving the dissolution rate of a sparingly soluble drug, loaded on its surface. Nifedipine, which has a very low water solub...

The purpose of this paper is to describe the preparation of a microcomputer program for the simulation of plasma levels. The program, which is very flexible and user friendly, should assist formulators in the design of modified-release dosage forms

A previous paper dealt with the preparation of an in vitro programmable zero-order drug delivery system in which the area of the surface exposed to the dissolution medium and the macromolecular relaxation of polymer controlled the release of the drug. In the present study, the preparation of similar delivery systems is described, in which differing...

Differential scanning calorimetry has been applied to the study of the solid system cross-linked polyvinylpyrrolidone/trimethoprim. Different results have been systematically obtained on co-ground and not co-ground mixtures, suggesting some type of interaction to take place between components as a consequence of co-grinding. A simple phenomenologic...

Water uptake and disintegrating force development have frequently been related to tablet disintegration properties. Water penetration into compressed tablets has been studied by many authors using modified Enslin apparatus. Meanwhile, in previous papers by our group, a great deal of attention has been paid to the measurements of disintegrating forc...

A method based on DSC measurements which allows the determination of the stoichiometry of a drug-cyclodextrin complex has been developed. A practical example on the vinburnine-gammacyclodextrin complex isolated by the authors is presented and discussed.

Disintegration of compacts in the presence of a solvent is followed by measurement of the disintegration force development as a function of time. The process is described by the delamination of the compact and the rate of expansion of the detached layers using a new equation. © 1987 Springer-Verlag.

The bioavailability of a new controlled release formulation of indomethacin lysine salt in tablets was tested in 6 healthy humans against a conventional indomethacin lysinate formulation in capsules. Both contained 100 mg of the drug, i.e. 70 mg indomethacin. Peak plasma levels were lower and more lasting and the AUC was higher with the new control...

Some coated aspirin tablet formulations were evaluated by relating their properties to disintegrating force development patterns. The treatment of disintegrating force-time curves was effected using the Weibull distribution as proposed for dissolution. Such parameters as the maximum disintegrating force developed, the time needed to reach 63.2% max...

Thermal analysis of the binary system benzoic acid (BA) and trimethoprim (TMP) provided evidence of the formation of two molecular compounds. BA-TMP and two crystalline forms of (BA)2-TMP were characterized on the basis of their thermodynamic parameters as well as of crystallographic and spectroscopic properties. The availability of these compounds...

The kinetic aspects of acid neutralization of three commercial antacid products in tablet form, based on different chemicals (hydrotalcite, a combination of magnesium and aluminium hydroxide and a mixture of carbonates), were investigated. The testing program included the A.N.C. test (according to U.S.P. XX), the Rosset-Rice test, and an acid react...

Urea complexes of 10-undecen-hydroxamic acid (III) and trans-2-dodecen-hydroxamic acid (IV) were prepared with the aim of testing antifungal activity. No significant difference of activity between the complexes and corresponding hydroxamic acids was demonstrated.

The influence of disgregants on the in vitro release characteristics of coated acetylsalicylic acid (ASA) tablets was investigated in relation to the compression force applied during the preparation of tablets. Two rapidly disintegrating coated ASA formulations were prepared and the corresponding tablets checked for crushing strength, disintegratio...

Physico-chemical properties of sulfamethoxazole-trimethoprim 1:1 molecular compound were investigated by DSC, X-ray diffraction patterns and I.R. spectroscopy. The phase diagram of the binary system was drawn and the possible nature of bonding between the components was briefly discussed.

Circular dichroism curves are reported for a number of aralkylamines having a general formula R--CH(NH2)--R' (in which R and R' are alkyl-, aryl- or aralkyl-groups) and for 1-aminobenzocyclobutene, 1-aminoindane, 1-amino-1,2,3,4-tetrahydronaphthalene and 2-amino-1,2,3,4-tetrahydronaphthalene. The Cotton effects due to aromatic chromophore 1Lb and 1...

Circular dichroism curves have been measured for phthaloyl-, maleyl- and itaconyl-derivatives of a number of amines having a general formula R--CH(NH2)--R' (in which R and R' are alkyl-, aryl- or cyclohexyl-groups) and of 1,2,3,4-tetrahydro-1-naphthylamine and 1,2,3,4-tetrahydro-2-naphthylamine. We conclude that the determination of absolute config...

In order to assess the influence of crystalline form on direct compression of SMD, three SMD II formulations, having the same composition as the previously investigated SMD I(a) formulations, were prepared and examined. The compression characteristics of formulations were evaluated by such parameters as ratio of bottom and top punch pressure (R), e...

Bei der Umsetzung der Aminoketone (I) bzw. (IV) mit Benzylchlorid in Gegenwart von Natriumäthylat erhält man die benzylierten Verbindungen (II) und (III) bzw. (V) und (VI).

Alkyl-a-brom-3,4-dimethyl-acetophenone, z.B. (I), werden mit Isopropylamin in die entsprechenden N-Isopropylamino-ketone, z.B. (II), übergeführt.