Influence of the viscosity grade and the particle size of HPMC on metronidazole release from matrix tablets

Campos-Aldrete, Ma. Elena; Villafuerte-Robles, Leopoldo

doi:10.1016/s0939-6411(96)00004-5

Cited by 105 publications

(42 citation statements)

References 10 publications

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“…Thus, at low polymer load the faster hydration of HPMC type 2208 resulted in a faster formation of the matrix and at both polymer loads the higher viscosity of HPMC formed a more tortuous and resistant barrier to diffusion and erosion, resulting in slower release rates. These results are in accordance with dissolution studies of HPMC after direct compression and batch granulation [4,9,12,14,41,43,45,46]. The particle size of theophylline starting material did not influence the release of the formulations.…”

Section: Influence Of the Formulation Variables On Tablet Qualitysupporting

confidence: 87%

“…Tablets with HPMC can be produced by direct compression but often granulation is necessary [4,9]. High shear and fluid bed granulation were successfully applied to improve the flowability of formulations with HPMC [4,5,9,[10][11][12][13][14][15][16], often requiring hydro-alcoholic granulation liquids as granulation with water yielded lumps as well as fines due to the irregular wetting of the formulation.…”

Section: Introductionmentioning

confidence: 99%

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Continuous twin screw granulation of controlled release formulations with various HPMC grades

Vanhoorne

Janssens

Vercruysse

et al. 2016

International Journal of Pharmaceutics

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HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation.The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24 h with release profiles close to zero-order.The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC.

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Section: Influence Of the Formulation Variables On Tablet Qualitysupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Continuous twin screw granulation of controlled release formulations with various HPMC grades

Vanhoorne

Janssens

Vercruysse

et al. 2016

International Journal of Pharmaceutics

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“…The solubility of MTZ in water is reported to be 10 mg/ml, 32) which is less than desired solubility requirement (50-300 mg/ml) for osmotic delivery system. 30) In order to get the desired release from the developed formulation SLS was added in core formulation to modulate the solubility of MTZ within the core.…”

Section: Resultsmentioning

confidence: 93%

Colon Targeted Delivery Systems of Metronidazole Based on Osmotic Technology: Development and Evaluation

Kumar

Singh

Mishra

2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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Metronidazole (MTZ) is the most preferred choice of drugs for intestinal amoebiasis.1) This drug is to be delivered to the colon for its effective action against Entamoebe histolytica wherein the trophozoites reside in the lumen of the caecum and large intestine and also adhere to the colonic mucus and epithelial layers.2) But the pharmacokinetic profile of metronidazole indicates that the drug is completely and promptly absorbed after oral administration and plasma concentration of about 10 mg/ml is reached approximately 1 h after a single 500 mg dose.3) The administration of this drug in conventional tablet dosage form provides minimal amount of metronidazole for local action in the colon, still resulting in the relief of amoebiasis, but with unwanted systemic effects. Thus there is strong clinical need and market potential for a delivery system that will deliver maximum amount of MTZ to the colon in controlled manner.Colon targeted delivery systems are well recognized and documented to deliver most of the drugs to colon. In the past, various primary approaches for colon targeted delivery, such as, prodrugs approach, 4) pH, 5) and time 6) and pressure dependent systems, 7) have achieved limited success. The majority of these systems, developed during the past decade, were based on pH and time dependent mechanisms with limited in-vivo evaluation.8) Minor variation in pH between the small intestine and the colon makes the pH-dependent systems less specific, in terms of targeted release in the colon. Time-dependent systems predominantly depend on the transit time of the delivery system in the gastrointestinal tract (GIT). A major limitation with these systems is that in vivo variation of the small intestinal transit time may lead to release of the drugs in the small intestine or terminal part of the colon. 9,10)The patho-physiological state of an individual will have a significant impact on the performance of these time-dependent systems. Patients with irritable bowel syndrome and ulcerative colitis exhibited accelerated transit through different regions of the colon. 11,12)The best alternative approach for colon specific drug delivery is the use of carriers that are degraded exclusively by colonic bacteria. Most of the carrier based systems provide controlled delivery of drugs in matrix and/or reservoir type systems, which pose problems of bioavailability fluctuation due to pH variations. 13,14) Moreover, the release of drugs from matrix and/or reservoir type systems is affected by hydrodynamic conditions of the body.Osmotic drug delivery system (ODDS) utilizes the principle of osmotic pressure for controlled delivery of drugs. 15)Drug release from these systems is independent of pH and other physiological parameter to a large extent and exhibit significant in vitro-in vivo correlation.16) Drug delivery from ODDS follow zero-order kinetic hence provides better control over in-vivo performance. Various types of osmotic pumps have been reported to target the drug to colon for local or systemic therapy. [17][18][19...

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“…It was reported that polymers with higher viscosities retarded drug release to a greater extent than lower viscosity polymers (24). The possible mechanism behind the rapid release rate produced by SAL matrices was rapid wetting during the dissolution test, forming a loose and porous outer gel layer that was easily eroded, resulting in a higher drug release rate due to enhanced mobility of macromolecules causing greater diffusivities of dissolution medium and drug (25).…”

Section: In Vitro Drug Releasementioning

confidence: 99%

Some variables affecting the characteristics of Eudragit E-sodium alginate polyelectrolyte complex as a tablet matrix for diltiazem hydrochloride

Yusif¹,

Hashim²,

El-Dahan³

2014

Acta Pharmaceutica

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Modification of polymer properties can be achieved by copolymerization or derivatization, a strategy that was successfully applied in the past. However, this approach has the major drawback that new chemical entities are introduced with an unknown toxicological profile. Before these products can be evaluated in animals and also in human clinical trials, a lot of time and resources must be spent to assess their safety. To overcome this problem, physical modification of the polymer, rather than chemical, is a sound approach. In this respect, polyelectrolyte complexes (PECs) may provide a valuable tool to design drug delivery systems with specific physicochemical properties. PECs obtained Eudragit E (EE)-sodium alginate (SA) polyelectrolyte complexes (PECs) were prepared at pH 4 and 5.8 using sodium alginate of high (SAH) and low viscosity (SAL). The optimum EE-SA complexation mass ratio was determined using viscosity measurements. Interactions between EE and SA in PECs were characterized by Fourier transform infra-red spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Diltiazem hydrochloride (DTZ HCl) tablets were prepared using the prepared EE-SA PECs and their physical mixtures at different ratios as matrices. Tablets were evaluated for swelling characteristics and in vitro drug release. Tablets containing EE-SAH physical mixtures of ratios (1.5:1 and 1:3) as matrices were effective in achieving sustained release of DTZ HCl, where the percent drug released was significantly (p < 0.05) decreased compared to that from tablets either containing the same ratios of EE-SAL physical mixtures or the preformed EE--SAH and EE-SAL PECs.

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Influence of the viscosity grade and the particle size of HPMC on metronidazole release from matrix tablets

Cited by 105 publications

References 10 publications

Continuous twin screw granulation of controlled release formulations with various HPMC grades

Continuous twin screw granulation of controlled release formulations with various HPMC grades

Colon Targeted Delivery Systems of Metronidazole Based on Osmotic Technology: Development and Evaluation

Some variables affecting the characteristics of Eudragit E-sodium alginate polyelectrolyte complex as a tablet matrix for diltiazem hydrochloride

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