Pharmacoscintigraphic evaluation of a modified release (Geomatrix®) diltiazem formulation

Wilding, Ian R.; Davis, S.S.; Sparrow, Robert; Ziemniak, J; Heald, Donald

doi:10.1016/0168-3659(94)00066-4

Cited by 26 publications

(10 citation statements)

References 19 publications

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“…It is known that diltiazem is uniformly absorbed throughout the GI tract and is absorbed in the human colon. 27) In our study, diltiazem at high doses was also well absorbed in the colon. However, colonic absorption decreased at low doses even though diltiazem is a Class 1 compound.…”

Section: Resultsmentioning

confidence: 65%

The Relationship between the Drug Concentration Profiles in Plasma and the Drug Doses in the Colon

Tajiri

Kanamaru

Yoshida

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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After the dosing of an extended-release (ER) formulation, compounds may exist in solutions at various concentrations in the colon because the drugs are released at various speeds from the ER dosage form. The aim of this study was to investigate the relationship between the drug concentration profiles in plasma and the drug doses in the colon. Several drug solutions of different concentrations were directly administered into the ascending colon of dogs using a lubricated endoscope, and the effects of the drug dose on colonic absorption were estimated. As a result, dose-dependency of colonic absorption varied from compound to compound. Although the relative bioavailability of colonic administration of diclofenac, metformin and cevimeline compared to oral administration was similar regardless of the drug doses in the colon, colonic absorption of diltiazem varied according to the doses. From the results of the co-administration of verapamil and fexofenadine, it was clear that diltiazem underwent extensive hepatic and gastrointestinal first-pass metabolism, resulting in a low area under the curves (AUC) at a low drug dose. During the design of oral ER delivery systems, a colonic absorption study of candidate compounds should be carried out at several solutions of different drug concentrations and assessed carefully.

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Section: Resultsmentioning

confidence: 65%

The Relationship between the Drug Concentration Profiles in Plasma and the Drug Doses in the Colon

Tajiri

Kanamaru

Yoshida

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…18,19 The capsules may have been located in the less muscular body of the stomach and not propelled into the antrum of the stomach so that emptying could take place. The interdigestive motility patterns would also have been disrupted when lunch was given, an effect observed in previous studies 20 resulting in further prolongation of gastric residence.…”

Section: Resultsmentioning

confidence: 78%

Scintigraphic Evaluation of a New Capsule-Type Colon Specific Drug Delivery System in Healthy Volunteers

Ishibashi

Pitcairn²,

Yoshino

et al. 1998

Journal of Pharmaceutical Sciences

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Colonic drug delivery is intended for local or systemic therapies. The lack of predictive in vitro or animal model leads to considerable time delays in colonic product development. The objective of this scintigraphic study was to provide "proof of concept" for a novel capsule-type colonic delivery system (Colon-Targeted Delivery Capsule) in healthy volunteers. The human data validates the design concept behind the release mechanism, in that capsule disintegration, and hence drug release, did not start until 5 h after gastric emptying, irrespective of whether the product was administered to fasted or fed subjects. However, the potential for prolonged gastric residence for large enteric coated products intended for intestinal targeting was also observed; overall, the study provides a focus for subsequent product development and highlights the role of scintigraphy in dynamically visualizing the drug delivery process.

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“…This observation is characteristic of the continuous feeding regimens used in this study in which the stomach always remains in the fed state, with the onset of interdigestive motility patterns being arrested by lunch and, in some individuals, by dinner. 9 In cases of prolonged gastric residence (subjects 1, 3, 4, and 7), total tablet disintegration occurred in the gastric contents, and the remnants were emptied from the stomach along with the solid phase of the food.…”

Section: August Supplement 7smentioning

confidence: 99%

“…8 Prior to the scintigraphic study itself, appropriate validation measurements are performed in vitro to show that the labeling procedure does not compromise the performance of the formulation or the stability of the drug.A new once-a-day MR formulation of diltiazem (DTZ) for the treatment of hypertension has been produced by Rhone-Poulenc Rorer using the Geomatrix ® technology (SkyePharma Plc), which consists of a swelling trilayered tablet. 9 In vitro data indicate that after 24 hours, the tablet increases from approximately 7 mm to a diametepr of 14 to 15 mm. The rate and duration of drug release from the Geomatrix ® system are regulated by the exposed surface area and the volume dimension of the core.…”

mentioning

confidence: 99%

Visualization of Product Performance in the Gut: What Role in the Drug Development/Regulatory Paradigm?

Wilding¹,

Heald²

1999

The Journal of Clinical Pharma

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Pharmacoscintigraphic evaluation of a modified release (Geomatrix®) diltiazem formulation

Cited by 26 publications

References 19 publications

The Relationship between the Drug Concentration Profiles in Plasma and the Drug Doses in the Colon

The Relationship between the Drug Concentration Profiles in Plasma and the Drug Doses in the Colon

Scintigraphic Evaluation of a New Capsule-Type Colon Specific Drug Delivery System in Healthy Volunteers

Visualization of Product Performance in the Gut: What Role in the Drug Development/Regulatory Paradigm?

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