An in vitro investigation into the suitability of pH-dependent polymers for colonic targeting

Ashford, Marianne; Fell, John T.; Attwood, David; Sharma, H.L.; Woodhead, Philip J.

doi:10.1016/0378-5173(93)90344-f

Cited by 155 publications

(57 citation statements)

References 6 publications

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“…This was attributed by the disappearance of the tablet as shown in X-ray image Figure 4 (F). These results are in agreement with the results of Ashford et al (1993) who observed that the gastric emptying time of 0.6-2.9 hour, small intestine transit time of 1.8-8.5 hours and colonic arrival time of 3.2-9.8 hours while evaluating pectin as a compression coat for colonic drug delivery, using gamma scintigraphy.…”

Section: Resultssupporting

confidence: 82%

“…The various approaches that have been studied for targeting orally administered drugs to the colon include use of pH sensitive polymers, time dependent dosage forms and the use of carriers degraded by the enzymes produced by colonic bacteria (Ashford et al, 1993;Rama Prasad et al, 1998). Of these approaches, the use of materials that are degraded by the colonic microflora has been found to be the most promising because of their site specificity (Potts et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Formulation, in vitro drug release and in vivo human X-ray investigation of polysaccharide based drug delivery systems for targeting 5-fluorouracil to the colon

Chickpetty¹,

Raga²

2013

Braz. J. Pharm. Sci.

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The purpose of this research study was to develop 5-fluorouracil compression coated tablets by using biodegradable polysaccharide polymer locust bean gum (LBG) and hydroxyl propyl methyl cellulose (HPMC) as coating materials. The fast disintegrating core tablets containing 50 mg of 5-fluorouracil were compression coated with LBG and HPMC in different ratios (8:1, 7:2 and 6:3) with a coat weight of 300, 400 and 500 mg. In vitro dissolution data indicated that the formulation (CLH63) with a coat weight of 500 mg containing LBG and HPMC in the ratio 6:3 gave the best release profile (0% in first 5 hour and 96.18% in 24 hours). DSC and FTIR results indicated no possibility of interaction between drug and polymers or other excipients. In vivo human X-ray studies revealed that formulation CLH63 was able to resist breakdown in the stomach and small intestine. The disintegration of the tablet occurred in the colon between 8 to 16 hours of post dose. By the present study, it can be concluded that the LBG and HPMC based compression coated tablets of 5-fluorouracil will be useful strategy for colonic delivery of 5-fluorouracil without being released in upper gastrointestinal region for the safe and effective management of colon cancer. O propósito desta pesquisa foi desenvolver comprimidos revestidos de fluoruracila utilizando polissacarídio biodegradável polymer locust bean gum (LBG) e hidroxipropilmetil celulose (HPMC) como materiais de revestimento. Os comprimidos de desintegração rápida contendo 50 mg de fluoruracila foram revestidos por compressão com LBG e HPMC em diferentes proporções (8:1, 7:2 e 6:3), com peso de cobertura de 300, 400 e 500 mg. Os dados da dissolução in vitro indicaram que a formulação (CLH63) com peso de cobertura de 500 mg contendo LBG e HPMC na proporção de 6:3 forneceu o melhor perfil de liberação (0% nas primeiras 5 horas e 96,18% em 24 horas). Os resultados de DSC e de FTIR não indicaram interação entre o fármaco e os polímeros ou outros excipientes. Os estudos de raios X in vivo revelaram que a formulação CLH63 foi capaz de resistir à quebra no estômago e no intestino delgado. A desintegração do comprimido ocorreu no cólon, entre 8 e 16 horas após a administração da dose. Pelo presente estudo, concluiu-se que os comprimidos de fluoruracila revestidos com LBG e HPMC por compressão se constituirão em estratégia útil na liberação de fluoruracila no cólon, para o tratamento seguro e efetivo do câncer de cólon, sem que o fármaco seja liberado na região gastrointestinal superior. Unitermos:Comprimido de revestimento por compressão. Locust bean gum. Direcionamento para o cólon. Fluoruracila. Câncer de colon e raios X.

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Section: Resultssupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Formulation, in vitro drug release and in vivo human X-ray investigation of polysaccharide based drug delivery systems for targeting 5-fluorouracil to the colon

Chickpetty¹,

Raga²

2013

Braz. J. Pharm. Sci.

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“…A particular challenge in the pharmaceutical field is the development of a site-specific delivery system that could control delivery time for the release of active ingredient in the lower part of the small intestine, or in the colon. The approaches used in achieving colonic delivery of drugs include the use of prodrugs, 1,2 pH-sensitive polymer coating, 3,4 and time-dependent formulations. 5,6 In addition, the use of biodegradable polymers such as azopolymer and polysaccharide (eg, pectin and dextrin) for colon targeting are also reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting

et al. 2007

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An objective of the present investigation was to prepare and evaluate Eudragit-coated pectin microspheres for colon targeting of 5-fluorouracil (FU). Pectin microspheres were prepared by emulsion dehydration method using different ratios of FU and pectin (1:3 to 1:6), stirring speeds (500-2000 rpm) and emulsifier concentrations (0.75%-1.5% wt/vol). The yield of preparation and the encapsulation efficiencies were high for all pectin microspheres. Microspheres prepared by using drug:polymer ratio 1:4, stirring speed 1000 rpm, and 1.25% wt/vol concentration of emulsifying agent were selected as an optimized formulation. Eudragit-coating of pectin microspheres was performed by oil-in-oil solvent evaporation method using coat:core ratio (5:1). Pectin microspheres and Eudragit-coated pectin microspheres were evaluated for surface morphology, particle size and size distribution, swellability, percentage drug entrapment, and in vitro drug release in simulated gastrointestinal fluids (SGF). The in vitro drug release study of optimized formulation was also performed in simulated colonic fluid in the presence of 2% rat cecal content. Organ distribution study in albino rats was performed to establish the targeting potential of optimized formulation in the colon. The release profile of FU from Eudragit-coated pectin microspheres was pH dependent. In acidic medium, the release rate was much slower; however, the drug was released quickly at pH 7.4. It is concluded from the present investigation that Eudragit-coated pectin microspheres are promising controlled release carriers for colon-targeted delivery of FU.

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“…6) There are various problems with pH dependent drug delivery; however the pH in the gastrointestinal tract varies between and within individuals. [7][8][9] It is affected by diet and disease. 10) During acute stage of inflammatory bowel disease colonic pH has been found to be significantly lower than normal.…”

mentioning

confidence: 99%

Formulation and Evaluation of Press Coated Tablets for Pulsatile Drug Delivery Using Hydrophilic and Hydrophobic Polymers

Rane

Gattani

Kadam

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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Pulsatile drug delivery systems (PDDS) are gaining importance as these systems deliver the drug at specific time as per the pathophysiological need of the disease, resulting in improved patient therapeutic efficacy and compliance. These systems are beneficial for the drugs having chronopharmacological behaviour (where night time dosing is required), firstpass effect and having specific site of absorption in gastro intestinal tract (GIT). From the viewpoint of therapeutic optimization, maintaining a constant blood level for a drug in the human body is questionable.1) Long-term constant drug concentration exposed in blood and tissues may induce many problems such as tolerance of drug and activation of physiological system.2) Recently, chronotherapy has been extensively applied in clinical therapy by modulating the dosing regimen of drug administration according to physiological needs.3) Diseases wherein PDDS are promising include asthma, peptic ulcer, cardiovascular diseases, arthritis, and hypercholesterolemia. The pathophysiology of arthritis and patients with osteoarthritis tend to have less pain in the morning and more at night; while those with rheumatoid arthritis, have pain that usually peaks in the morning and decreases throughout the day. 4)A dry-coated tablet was recently renewed as a novel system to deliver a drug in a pulsatile way, at predetermined times following oral administration. 4,5) This novel system is not only rate controlled but is also time controlled. The dry-coated tablets were prepared by a direct compression method. This compression method eliminates the time-consuming and complicated coating or granulation processes and also improves the stability of the drug by protecting it from moisture. 6)There are various problems with pH dependent drug delivery; however the pH in the gastrointestinal tract varies between and within individuals. [7][8][9] It is affected by diet and disease.10) During acute stage of inflammatory bowel disease colonic pH has been found to be significantly lower than normal.11) In ulcerative colitis pH values 2.3-4.7 have been measured in the proximal parts of the colon.12)The purpose of this study was to develop press coated tablets for pulsatile drug delivery of ketoprofen. The oral press coated tablet was developed to achieve the time-controlled disintegrating or rupturing function with a distinct predetermined lag time. Press-coated tablet containing ketoprofen and other excipients in the inner core was formulated with an outer shell by different weight ratios of hydrophobic polymer (micronized ethylcellulose powder) and hydrophilic polymers (glycinemax husk, sodium alginate). Ethylcellulose (EC) is a well-known water-insoluble polymer that has been used as a rate-controlling membrane to regulate drug release. EC powder with different micronized sizes has been directly compressed to form compact EC in which plastic deformation is the predominant consolidation mechanism.13) Glycinemax containing dry matter (DM), crude protein (CP), crude fiber (CF), ether extract ...

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An in vitro investigation into the suitability of pH-dependent polymers for colonic targeting

Cited by 155 publications

References 6 publications

Formulation, in vitro drug release and in vivo human X-ray investigation of polysaccharide based drug delivery systems for targeting 5-fluorouracil to the colon

Formulation, in vitro drug release and in vivo human X-ray investigation of polysaccharide based drug delivery systems for targeting 5-fluorouracil to the colon

Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting

Formulation and Evaluation of Press Coated Tablets for Pulsatile Drug Delivery Using Hydrophilic and Hydrophobic Polymers

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