In this study hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) were used as polymeric carriers to improve controlled release performances of matrix tablets containing a ...soluble drug. The drug release behaviour of the systems containing these two polymers mixture and each material separately was investigated. To evaluate the effect of the dissolution medium pH, on the drug release performance, release tests were conducted at pH 1, 4.5 and 6.8. In vitro release studies demonstrated that the mixture of the two cellulose derivatives enables a better control of the drug release profiles at pH 4.5 and at 6.8 both in term of rate and mechanism. Texture analysis on the swollen tablets helps to understand drug release kinetic and mechanism. In fact, the results obtained confirm that a gel, which is characterized by high strength and consistence is less susceptible to erosion and chains disentanglement and the drug release mechanism is mainly governed by diffusion. On the contrary, gels, which show a low strength and texture, have low resistance to the fluid erosion action and the release of the active molecule is manly due to polymer relaxation and chains disentanglement moving the drug delivery kinetic towards an erosion/relaxation mechanism.
The aim of the present study is an investigation of the swelling behaviour of matrix systems containing a mixture of hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) with ...a model soluble drug to find the correlation between the morphological behaviour and the drug release performance. The swelling study was conducted on tablets containing only the drug and the two polymers mixture (MB) and on reference tablets containing each polymer and the same drug, at three different pHs. MB matrices show a similar swelling trend at pH 4.5 and 6.8, while they have different behaviour in acidic fluid. At pH 1 the gel layer formed by NaCMC is characterized by a rigid structure of a partially chemically crosslinked hydrogel while HPMC and MB matrices form a physical not crosslinked gel. At pH 4.5 and 6.8, all the systems show the typical morphological behaviour of a swellable matrix in which the macromolecular chains in the gel network are held together by weak bondings (physical gel). In these buffers, MB systems maintain a constant drug release rate coupling diffusion and erosion mechanism: the gel and infiltrated layers thicknesses are maintained constant and a zero-order release kinetics can be achieved.
Hydrophilic matrix tablets containing polyethylene oxides as the retarding polymer have been successfully employed in the controlled release of drugs. To evaluate the relative influence of drug ...diffusion and polymer erosion mechanisms in the drug delivery process, we studied the hydration behaviour of matrix tablets containing a water-soluble drug and PEOs of two different molecular weights: Polyox WSRN 1105 (
M
w=0.9×10
6) and Polyox WSRN 301 (
M
w=4×10
6). The hydration rate, the extent of swelling, and the erosion rate of matrices containing the polymer, the drug and tableting excipients were evaluated in comparison to tablets made of pure polymer. The results of these studies on function of the release behaviour were then discussed.
The results show that the higher molecular weight PEO swells to a greater extent and tends to form, upon hydration, a stronger gel, which is therefore less liable to erosion, if compared to the lower molecular weight PEO. This difference in the erosion behaviour can explain the different efficiencies of the two polymeric products in modulating the delivery rate of the water-soluble drug. Moreover, the presence of other soluble components (drug and excipients) in the dosage form enhances the erosion trend of the tablets with a consequent reduction of the efficiency of the polymer in drug release control.
A new chewing gum device in the form of a three layers tablet (
3TabGum) has been developed. The new drug delivery system is obtained, at room temperature, by direct compression using conventional ...pharmaceutical equipment. Basically, the resulting chewing gum tablets comprise a gum core combined with two protective antiadherent external layers, which prevent gum adhesion to the punches of the tableting machine. Drug release from a dosage form is the critical step in drug absorption and bioavailability, thus an experimental protocol has been designed to evaluate the efficiency of this kind of therapeutic system by verifying its capability to release the drug dose and by assessing the delivery rate. Simple diffusion into the medium causes the release of only a small percentage of the drug contained in the medicated chewing gum, while the delivery of the major part of the dose occurs during mastication. The results obtained in this study suggest that water soluble drugs are freely and easily released by chewing gums, while for actives characterized by reduced water solubility the release rate depends on the chewing time although all the drugs tested are completely released after a reasonable mastication time.
The aim of this work is to verify the efficiency of two kinds of matrix tablets formulations containing PEO or PVA as retarding polymer. Moreover, since in the last years the exposure to ionizing ...radiation is a more and more used method to reduce bacterial charge in pharmaceutical products, the effects of gamma irradiation on these two kinds of polymers has been evaluated. The study is performed on matrix tablets containing diltiazem HCl, as model drug, and polyethylene oxides (PEO) of two different molecular weights or polyvinylalchool (PVA) of medium degree of hydrolysis, as drug release modulators. Dissolution of the matrices, release of diltiazem and morphological behaviour of the samples, before and after exposure to increasing doses of gamma irradiation, are investigated in order to verify their stability.
The results show that the ionizing radiation does not modify significantly the dissolution trend of the PVA samples; on the contrary, the dissolution and the morphological behaviour of the PEO matrices is strongly affected by the radiation dose received. In particular, the dissolution rate of the irradiated PEO tablets dramatically increases as a function of the irradiation dose and the swelling process, which characterised the non-irradiated PEO samples, was replaced by a rapid erosion process responsible for the quickly dissolution of the matrices. The changes of the dissolution and morphological PEO tablets performances could be explained by a breaking of the polymeric chains (shown by EPR studies) as a consequence of the exposure to gamma rays. These chemical–structural modifications of the polymers are responsible for the reduced efficacy of the PEO systems in controlling the drug release rate.
A new biphasic release system for slightly soluble drugs has been proposed. To enhance the dissolution rate, the drug was milled with a superdisintegrant. Then, double-layer tablets were prepared. ...One layer was formulated to release the drug in a very short time (fast-release). The other consisted of an extended-release hydroxypropylmethylcellulose (HPMC) matrix. Different HPMC concentrations (10, 16 and 22%) and viscosity grades (Methocel K4, K15 and K100M) were used to obtain different release rates of the drug from the extended-release layer, ketoprofen and praziquantel were used as slightly soluble model drugs.The in vitro dissolution tests of the prepared double-layer systems, showed the desired biphasic behaviour: the drug contained in the fast releasing layer dissolved within the first 15 min, while the drug contained in the prolonged-release layer was released at different times, depending on the formulation of the hydrophilic matrix. In particular, an increase in the percentage and viscosity grade of HPMC, in the extended release layer, leads to a decrease in the drug delivery rate and produces a wide range of different release rates from only a few hours up to 24 h.
In recent years, the exposure to γ-radiation is an increasingly used method to sterilize or to reduce bacterial charge in drug-delivery devices. The aim of this study was to investigate whether the ...ionizing radiation may be responsible for drug inactivation or for the alteration of the functional excipient used to modulate drug release from a controlled-release delivery system. In this work, we investigated the physical and dissolution stability of prolonged release matrix tablets containing diltiazem hydrochloride, as a model drug, and hydroxypropylmethylcellulose (HPMC) of two different viscosity grades, as the retarding polymer, before and after exposure to increasing doses of γ-rays. The results show that γ-irradiation induces chemical modifications in the structure of the active agent, and also of the hydrophilic polymer. The electronic paramagnetic resonance analysis of γ-irradiated diltiazem has afforded evidence of carbon radicals stemming from C—H bond ruptures and sulphur radicals, the latter being formed mainly after admission of air at room temperature. The major radical products in the HPMC polymer radiolysis have been reckoned with chain scission events in agreement with the results of viscosity measurements that show a progressive decrease of the average molecular weight with increasing the radiation dose. The elaboration of the viscosity data has led to linear relationships between the η°/η ratio and the radiation dose D which were rationalized with the following equation under the assumption of a Mark-Houwink Sakurada coefficient a ≅ 1: η°/η = (1 + uy°D)a. In this equation, D is γ-radiation dose, η° and η are the reduced viscosities before and after the irradiation respectively, u is the number average degree of polymerization, and y° is the chain scission radiolytic yield. From the linear relationships G(chain scissions) = 1.2 × 10−6 and 1.4 × 10−6 moles/J have been obtained for the two HPMC polymer samples M100 and M4 of different molecular weight used in the experiments. These changes could be responsible for the alteration of the drug-release mechanism and reduced polymer efficacy in controlling drug release.
Orodispersible tablets (OTs) are uncoated tablets intended to be placed in the mouth where they disperse rapidly before being swallowed. The object of the present work is to develop an OT formulation ...able to disintegrate in less than 30s, characterized by acceptable technological properties and suitable for an industrial production. We tested how the characteristics of different direct-compression excipients can influence tablet disintegration and technological properties. The results show that mannitol guarantees the shortest disintegration time and the best technological and organoleptic properties. Starting from this excipient, to verify which is the effect of the tablets size and shape on the performance and the technological properties of the dosage form, an OT formulation, containing a slightly soluble non-steroidal anti-inflammatory drug has been scaled up preparing the tablets by direct compression and using punches of different size. The developed OT formulation maintains adequate organoleptic, technological characteristics and disintegration ability, sizes ranging from 6.5 to 13mm in diameter and it is possible to adapt this formulation to different production needs.
Photostability of extended-release matrix formulations Maggi, L.; Ochoa Machiste, E.; Fasani, E. ...
European journal of pharmaceutics and biopharmaceutics,
2003, 2003-Jan, 2003-01-00, 20030101, Volume:
55, Issue:
1
Journal Article
Peer reviewed
The photostability of drugs has been widely studied while less attention is devoted to the possible modifications that UV light may induce on the excipients of a dosage form, in particular, on the ...functional polymers used to modulate drug delivery. In this work we have evaluated the effect of UV light on the release characteristics of extended-release matrix tablets containing hydroxypropylmethylcellulose (HPMC) or polyethylene oxide (PEO) as retarding polymers. Two different model drugs have been used: nifedipine (insoluble and photolabile drug) and diltiazem (soluble and photostable drug). Photodecomposition of nifedipine was evaluated and the formation of the photoproducts was followed during the dissolution process. Regarding the dissolution stability, the matrix tablets containing HPMC exposed to UV light have not shown significant differences in drug release profiles compared to the same non-irradiated formulation, while the matrix tablets containing PEO and exposed to the same conditions of UV light have shown a remarkable increase of drug release rate within the first minutes of the dissolution test (burst effect) which is particularly critical because it can cause the loss of the desired therapeutic control.
Carbamazepine is an important anti-convulsant drug, characterized by a low water solubility. In order to improve its dissolution rate, drug:polymer systems were prepared using cross-linked ...polyvinylpyrrolidone (Polyplasdone XL®-10) as dissolution rate enhancer. The systems were obtained by mixing, milling and solvent evaporation.
The systems, characterized by improved drug dissolution rate, were studied by: Scanning Electron Microscopy (SEM), X-Ray Diffraction Powder (XRD), and Differential Scanning Calorimetry (DSC).
