Estimation of the percolation thresholds in acyclovir hydrophilic matrix tablets

Fuertes, Inmaculada; Miranda, Antonia; Millán, M.; Caraballo, Isidoro

doi:10.1016/j.ejpb.2006.05.009

Cited by 46 publications

(30 citation statements)

References 24 publications

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“…Its half-life is short (2-3 h) and its oral dosage forms must be administered five times during 24 h, leading to the patient incompliance. 6,7) Moreover, incomplete and variable GI absorption are two major problems in the efficacy of oral dosage forms.…”

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confidence: 99%

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Development and Evaluation of a Monolithic Floating Drug Delivery System for Acyclovir

Tavakoli

Varshosaz

Dorkoosh

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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Acyclovir (ACV), a model drug for this study, is one of the most effective drugs against viruses of the herpes group. Absorption of orally administered ACV is variable and incomplete, with a bioavailability of ca. 15-30%. The drug is absorbed in the duodenum after oral administration and hence, preparation of a floating drug delivery system (FDDS) for ACV may increase oral absorption of the drug. ACV matrix tablets (200 mg) containing an effervescent base (sodium bicarbonate and citric acid) and a binary combination of hydroxypropyl methylcellulose (HPMC) K4M with carbopol or sodium carboxymethyl cellulose (Na CMC) or polyvinylpyrrolidone (PVP) and/or sodium alginate were prepared by the direct compression method. The tablets were evaluated for physicochemical properties and in vitro floating ability (floating lag-time and duration), bioadhesiveness and drug release. The drug release studies were carried out in 0.1 N HCl (pH 1.2) at 37 0.5°C. At appropriate time intervals, samples were withdrawn and assayed spectrophotometrically at λ max 259 nm. The floating test showed tablets containing 15% effervescent base had a floating lag time of 10-30 s and a duration of floating time of 24 h. The formulations containing HPMC-PVP, HPMC-Na CMC, HPMC-carbopol, and HPMC-sodium alginate released about 60-90% of their drug content during a 12-h period. Increasing carbopol caused slower drug release. We concluded that the proposed tablets with 15% effervescent base, 20-30% HPMC, 30% Na CMC (and/or 20% PVP or 20% sodium alginate) showed good floating and drug release properties in vitro, and should be considered as FDDS for ACV.Key words acyclovir; floating drug delivery system; gastric residence time Considering their simple administration, oral drug dosage forms are the most commonly used drug delivery systems (DDS). The bioavailability of these dosage forms is affected by many different factors, of which one of the most important is their gastric residence time. In this respect, gastro retentive drug delivery systems (GRDDS), in which the drug is continuously released in the upper gastro-intestinal (GI), has attracted more attention in recent decades. Using GRDDS, many limitations of conventional oral dosage forms have been overcome. 1)Garg and Gupta 2) classified GRDDS into four main categories: a) gastric floating systems, b) expandable systems, c) bioadhesive systems and d) high density systems.Floating drug delivery systems (FDDS) consist mainly of two groups: 1) effervescent formulations, which produce carbon dioxide gas in contact with gastric contents, and 2) noneffervescent formulations which include hydrodynamically balanced systems, microporous systems, alginate beads, and hallow microsphere-microballoons.Moreover, superporous hydrogels and magnetic systems are categorized as gastric retaining oral delivery formulations. 2,3)FDDS offer various potential advantages for drugs which (i) have local gastric effects (such as misoprostol), (ii) are mainly absorbed in the stomach (e.g. furosemide), (iii) have an absorptio...

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confidence: 99%

“…Until now, various DDS of acyclovir, including matrix tablets, 7) microspheres, 8) and polymer films 9) have been developed for decreasing the frequency of administration of dosage form and increasing patient compliance.…”

mentioning

confidence: 99%

Development and Evaluation of a Monolithic Floating Drug Delivery System for Acyclovir

Tavakoli

Varshosaz

Dorkoosh

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Phase transition is related to the presence of the percolation threshold of one component of the formulation, and normally produces a significant change in release profiles (11,26).…”

Section: Drug Releasementioning

confidence: 99%

Critical points in ethylcellulose matrices: Influence of the polymer, drug and filler properties

Cifuentes¹,

Aguilar-de-Leyva²,

Rajabi‐Siahboomi³

et al. 2013

Acta Pharmaceutica

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Due to their simple and low-cost manufacturing process, matrix tablets are pharmaceutical dosage forms most widely used for the formulation of oral controlled release of drugs (1). These systems involve dispersion of one or more drugs in a support structure, which in the majority of the cases is of polymeric nature.Inert matrices are systems that consist of a polymeric porous solid network, which is insoluble and indigestible in the gastrointestinal tract (2). Drug release from these dosage forms occurs by drug diffusion through the pores of the matrices, including the initial pores and the pores that appear when the drug or soluble excipients have been dissolved (3).Ethylcellulose is a water insoluble polymer that has been used in the manufacturing of different solid oral dosage forms. It is used in the preparation of microcapsules and microspheres, as a barrier membrane in reservoirs, and as inert matrix-former for oral Percolation theory has been applied to study the drug release behaviour in multicomponent inert matrices containing ethylcellulose as a matrix forming polymer. Global influence of major formulation factors such as polymer viscosity, polymer particle size, drug and filler solubility and porosity of the tablets in drug release kinetics has been studied for the first time. Batches containing three viscosity grades of Ethocel™, microcrystalline cellulose (MCC) and lactose as fillers, a lubricant and flow aid mixture and three drugs with different solubility have been manufactured. For some batches, compression pressure was varied in order to obtain matrices with five levels of initial porosity. The behaviour of inert matrices was explained based on the percolation ranges of the main components of the formulation. The effect of the porosity percolation threshold was observed and the existence of a tricoherent drug-polymer-filler system is hypothesized.

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“…Percolation theory represents a powerful concept which covers a wide range of applications in pharmaceutical technology (6). Previous works have demonstrated experimentally the influence of the particle size of the components on the percolation threshold in hydrophilic matrices, as well as the importance of the initial porosity in the formation of the gel layer (7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have shown that the existence of a sample-spanning cluster of excipient plus pores in the hydrophilic matrix before the matrix is placed in contact with the liquid, conditions for the release kinetics of the drug (7)(8)(9)(10)(11).…”

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Polymer Percolation Threshold in HPMC Extended Release Formulation of Carbamazepine and Verapamil HCl

2010

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Abstract. The principles of the percolation theory were applied to further understand and design hydroxypropyl methylcellulose (HPMC) extended release matrix tablets containing carbamazepine and verapamil HCl. This statistical theory studies disordered or chaotic systems where the components are randomly distributed in a lattice. The application of this theory to study the hydration and drug release of hydrophilic matrices allows describing the changes in hydration and drug release kinetics of swellable matrices. The aim of this work was to study and develop extended release matrix formulations for carbamazepine and verapamil HCl, containing hypromellose (HPMC, METHOCEL™ Premium K100M CR) as rate controlling polymer using the concepts of percolation theory. The knowledge of the percolation threshold of the components of the matrix formulations contributes to improve their design. First, reducing the time to market and second, avoiding to formulate in the nearby of the percolation threshold, which will result in a lower variability. Therefore these formulations will be more robust when they are prepared at industrial scale. The HPMC percolation threshold for drugs with very different water solubilities was determined and it was shown that there was no significant influence of drug solubility on the HPMC critical concentration threshold (excipient percolation threshold). This may be related to the versatility and broad functionality of the swelling hydrophilic matrices.

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Estimation of the percolation thresholds in acyclovir hydrophilic matrix tablets

Cited by 46 publications

References 24 publications

Development and Evaluation of a Monolithic Floating Drug Delivery System for Acyclovir

Development and Evaluation of a Monolithic Floating Drug Delivery System for Acyclovir

Critical points in ethylcellulose matrices: Influence of the polymer, drug and filler properties

Polymer Percolation Threshold in HPMC Extended Release Formulation of Carbamazepine and Verapamil HCl

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