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: 3.65). 10/1992; 86(1):79-88. 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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    • "Both effervescent and non effervescent systems of floating approach have been reported in literatures. (Hilton AK et al., 1992; Reddy LH et al., 2002; Bardonnet PL et al., 2006). "
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    ABSTRACT: Floating Drug delivery system is used to target the drug release in the stomach or to the upper parts of the intestine. The eradication of Helicobacter pylori requires the administration of various medicaments several times a day, which often results in poor patient compliance. More reliable therapy can be achieved by using FDDS which can be expected that the topical delivery of antibiotic through a FDDS may result in complete removal of the organisms in the fundal area due to bactericidal drug levels being reached in this area, and might lead to better treatment of peptic ulcer. Since gatifloxacin is a potential drug for eradication of H. Pylori infection responsible for gastric and duodenal ulcers, the oral delivery of antibiotic gatifloxacin was facilated by preparing a non-disintegrating floating dosage form which can increase its local availability in the stomach by increasing the drug's gastric residence time. The tablets were prepared in six batches F1 to F6 by the direct compression technique using polymers such as hydroxyl propylmethylcellulose (HPMC K4M, HPMCK 15M M, and HPMC K100M, along with sodium bicarbonate as the gas –generating agents. The prepared tablets were evaluated for their physicochemical properties and drug release. In-vitro release studies indicated that the gatifloxacin release form the floating dosage form was uniform F2 and F6 and followed Higuchi drug release. Sodium bicarbonate was used as the gas-generating agents which cause the tablets to float on the G.I fluids. Formulation showed a floating lag time less than 60 seconds and floating time above 12 hrs. INTRODUCTION Gastric emptying of dosage forms is an extremely variable process and ability to prolong and control the emptying time is a valuable asset for dosage forms, which reside in the stomach for a longer period of time than conventional dosage forms (S.S. Patel et al., 2006). Several difficulties are faced in designing controlled release systems for better absorption and enhanced Corresponding Author
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    • "Therefore, it is necessary to design drug delivery systems that not only alleviate the shortcomings of conventional delivery vehicles but also deliver amoxicillin to the infected cell lines. Some researchers had prepared and reported new amoxicillin formulations, such as floating tablets [3] [4], mucoadhesive tablets [5], and mucoadhesive microspheres [6], which were able to reside in stomach for an extended period for more effective H. pylori eradication. Amongst the described formulations, the floating tablet is preferred for better and less variable gastric retention, but it has a limitation of incorporation of high dose of the drug. "
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    ABSTRACT: Purpose. Effective Helicobacter pylori eradication requires delivery of the antibiotic locally in the stomach. High dose of amoxicillin (750 to 1000 mg) is difficult to incorporate in floating tablets but can easily be given in liquid dosage form. Keeping the above facts in mind, we made an attempt to develop a new floating in situ gelling system of amoxicillin with increased residence time using sodium alginate as gelling polymer to eradicate H. pylori. Methods. Floating in situ gelling formulations were prepared using sodium alginate, calcium chloride, sodium citrate, hydroxypropyl methyl cellulose K100, and sodium bicarbonate. The prepared formulations were evaluated for solution viscosity, floating lag time, total floating time, and in vitro drug release. The formulation was optimized using a 3(2) full factorial design. Dissolution data were fitted to various models to ascertain kinetic of drug release. Regression analysis and analysis of variance were performed for dependent variables. Results. All formulations (F(1)-F(9)) showed floating within 30 s and had total floating time of more than 24 h. All the formulations showed good pourability. It was observed that concentration of sodium alginate and HPMC K100 had significant influence on floating lag time, cumulative percentage drug release in 6 h and 10 h. The batch F(8) was considered optimum since it showed more similarity in drug release (f(2) = 74.38) to the theoretical release profile. Conclusion. Floating in situ gelling system of amoxicillin can be formulated using sodium alginate as a gelling polymer to sustain the drug release for 10 to 12 h with zero-order release kinetics.
    07/2011; 2011:276250. DOI:10.5402/2011/276250
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    • "tract for an extended period of time for a more effective treatment [16] [17]. This would lead to improvement in the bioavailability of the drug. "
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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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