In vitro and in vivo evaluation of an oral sustained-release floating dosage form of amoxycillin trihydrate

Department of Pharmaceutics, Trinity College, University of Dublin, Shrewsbury Road, Dublin 4, Ireland
International Journal of Pharmaceutics (Impact Factor: 3.79). 10/1992; DOI: 10.1016/0378-5173(92)90033-X

ABSTRACT Various hydrophilic polymers were investigated for the preparation of amoxycillin trihydrate sustained-release (SR) tablets. The most suitable system contained a 1:2 ratio of hydroxypropylcellulose (HPC) to drug, which compressed easily and was not affected by alteration in normal compaction pressure. Intrinsic dissolution studies at pH 2 showed that reduction in drug loading decreased drug release, which being linear with time was characteristic of an eroding matrix with a hydrated layer. Examination of compacts over a wider range of pH showed the slowest rate of drug release at pH 6, corresponding to minimum solubility of the drug. Further formulation to enhance gastric retention time (GRT), by incorporation of a gas-generating system, yielded either bilayer tablets which prematurely failed or large single-layer tablets which remained buoyant for 6 h and had satisfactory in vitro SR. However, when the latter tablets were compared against conventional capsules in fasted humans at 500 mg equivalent dose of amoxycillin, their relative bioavailability was reduced to 80.5% and other pharmacokinetic parameters indicated lack of improved efficacy.

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    ABSTRACT: An attempt has been made to develop a gastroretentive sustained release delivery system with swellable and mucoadhesive properties for a drug like amoxycillin that has gives localised action along with the added advantage of a common side effect like disturbance of colonic bacteria. Hydrophilic polymers like poly (ethylene oxide), hydroxypropyl cellulose and hydroxypropylmethyl cellulose were tried in combinations and statistically optimised. Formulations were evaluated for in vitro drug release profile, swelling characteristics and in vitro mucoadhesion property. Stability study was carried out to ensure the complete characterisation of the formulation. Gastroretentive ability was assured by in vivo study of non medicated tablet formulations by X-ray method. A 3 2 factorial design was used to optimize the formulation to get the release profile for upto 24 h. The in vitro drug release followed Weibull kinetics and the drug release mechanism was found to be of anomalous or non-Fickian type. The high water uptake leading to higher swelling of the tablet supported the anomalous release mechanism of amoxycillin. Also the mucoadhesion property values were satisfying. A formulation can be developed using swellable mucoadhesive biopolymers, which show excellent adhesion and gastroretention and desired release profiles thus providing temporal and spatial control.
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    ABSTRACT: The aim of this work was to design and evaluate effervescent floating gastro-retentive drug delivery matrix tablets with sustained-release behavior using a binary mixture of hydroxyethyl cellulose and sodium alginate. Pentoxifylline was used as a highly water-soluble, short half-life model drug with a high density. The floating capacity, swelling, and drug release behaviors of drug-loaded matrix tablets were evaluated in 0.1 N HCl (pH 1.2) at 37°C±0.5°C. Release data were analyzed by fitting the power law model of Korsmeyer-Peppas. The effect of different formulation variables was investigated, such as wet granulation, sodium bicarbonate gas-forming agent level, and tablet hardness properties. Statistical analysis was applied by paired sample t-test and one-way analysis of variance depending on the type of data to determine significant effect of different parameters. All prepared tablets through wet granulation showed acceptable physicochemical properties and their drug release profiles followed non-Fickian diffusion. They could float on the surface of dissolution medium and sustain drug release over 24 hours. Tablets prepared with 20% w/w sodium bicarbonate at 50-54 N hardness were promising with respect to their floating lag time, floating duration, swelling ability, and sustained drug release profile.
    Drug Design, Development and Therapy 01/2015; 9:1843-57. DOI:10.2147/DDDT.S78717 · 3.03 Impact Factor
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    ABSTRACT: INTRODUCTION An important prerequisite for successful performance for an oral extended release drug delivery system is that the drug should have good absorption throughout the whole gastrointestinal tract (GIT) to ensure continuous absorption of released drug. But for large number of drugs, transport across the intestinal epithelium in each segment of GIT is not uniform and often limited to a particular segment (window) only. So, the oral extended release drug delivery becomes more difficult due to the inability to restrain and localize the drug delivery system within the desired region of GIT. These aspects lead to development of a drug delivery system which will remain in the stomach for a prolonged and predictable time. One of the most feasible approaches for this in the GIT is to control GRT using GRDF that will provide us with new and important therapeutic options. [1, 2] The retention of oral dosage forms in the upper GIT causes prolonged contact time of drug with the GI mucosa, leading to higher bioavailability and hence therapeutic efficacy, reduced time intervals for drug administration, potentially reduced dose size and thus improved patient compliance. [3-5] Several approaches have been reported for controlling the residence time of a drug delivery system in a particular region of the gastrointestinal tract, such as gastric floating systems, high density systems, mucoadhesive systems, magnetic systems, unfoldable, extendable, or expandable systems and super porous, biodegradable hydrogel systems. [1, 2] Floating drug delivery system or hydrodynamically balanced systems (HBS) have a bulk density lower than gastric fluids (i.e. 1.004 g/cm 3) and therefore remain floating in the stomach unflattering the gastric emptying rate for a prolonged period. The drug is slowly released at a desired rate from the floating system and after the complete release the residual system is expelled from the stomach. This leads to an increase in the GRT and a better control over fluctuations in plasma drug concentration. [1, 3, 6] Hydrophilic polymers like hydroxypropyl methyl cellulose (HPMC) are widely used in oral controlled drug delivery because they make it easier to achieve a desirable drug release profile. [2] Effervescent floating delivery systems employ matrices from swelling polymers like methocel or chitosan and effervescent components such as sodium bicarbonate and tartaric or citric acid or matrices having chambers of liquid components that gasify at body temperature. The matrices are prepared in such a manner that when they come in contact with stomach fluid, carbon dioxide is generated and retained entrapped in the hydrocolloid gel. This leads to an upward drift of the dosage form and maintains it in a floating condition. [6] FDDS is also appropriate for drugs with an absorption window in the stomach or in the initial portion of the small intestine such as furosemide and theophylline, for drugs that are unstable in the intestinal fluid such as captopril and for drugs that exhibit poor solubility in the intestinal tract such as diazepam and verapamil HCl. [7] Rosuvastatin calcium is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, used to treat high cholesterol and related conditions and to prevent cardiovascular disease. The bioavailability of rosuvastatin calcium following oral administration is about 20%; [8] thus a sustained release dosage form of Rosuvastatin calcium is desirable. Rosuvastatin calcium is rapidly but incompletely absorbed from the GIT with peak concentrations in plasma occurring about 5 hours after administration by mouth. [8] These properties of rosuvastatin calcium do not favor the traditional approach to sustain release delivery, as in the traditional approach; the sustained release product is designed to release the drug over the entire GIT. Hence,