Oral product input to the GI tract: GIS an oral product performance technology

doi:10.1007/s11705-017-1658-7

Front. Chem. Sci. Eng.

2017, Vol. 11

Issue (4) : 516-520 https://doi.org/10.1007/s11705-017-1658-7

VIEWS & COMMENTS

Oral product input to the GI tract: GIS an oral product performance technology

Gordon L. Amidon(

), Yasuhiro Tsume

College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA

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Abstract

The patient receives a pharmaceutical product, not a drug. The pharmaceutical products are formulated with a drug, an active ingredient to produce the maximum therapeutic effect after oral absorption. Therefore, it is the product we must optimize for the patients. In order to assure the safety and efficacy of pharmaceutical products, we need an in vivo predictive tool for oral product performance in patients. Currently, we are a surprisingly long way from accomplishing that objective. If the 20th century was the ‘age of the drug’, i.e., the ‘magic bullet’, the 21st century must become the ‘age of the guided missile’, i.e., the delivery system, including the form of the active pharmaceutical ingredient (API) (‘drug’). The physical form of the drug and the delivery system must be optimized to maximize the therapeutic benefits of pharmaceutical products for humans. Oral immediate release (IR) dosage forms cannot be optimal for all drugs or likely even any drugs (APIs). Still, the formulation of pharmaceutical products has to be optimized for patients. But how do we optimize oral delivery of drugs? It is usually through ‘trial and error’, in humans! We need a better way to optimize the oral dosage forms. We have suggested to select different dissolution methodologies for this optimization based on BCS Subclasses. In this article, we present the predicted in vivo drug dissolution profile of ketoconazole as a model drug from our laboratory utilizing a gastrointestinal simulator (GIS), which is an adaptation of the ASD system. GIS consists of three chambers representing stomach, duodenum, and jejunum, to create the human gastrointestinal tract-like environment and enable the control the gastric emptying rate. This dissolution system allows the monitoring of the drug dissolution phenomena and the observation of the supersaturation and the precipitation of pharmaceutical products, which is useful information to predict in vivo dissolution of pharmaceutical products. This system can provide the actual input needed to accurately predict the input into the systemic circulation required by many of the absorption prediction packages available today.

Keywords GIS in vivo predictive dissolution ketoconazole BCS subclassification supersaturation

Corresponding Author(s): Gordon L. Amidon

Just Accepted Date: 10 May 2017 Online First Date: 28 July 2017 Issue Date: 06 November 2017

Cite this article:

Gordon L. Amidon,Yasuhiro Tsume. Oral product input to the GI tract: GIS an oral product performance technology[J]. Front. Chem. Sci. Eng., 2017, 11(4): 516-520.

URL:

https://academic.hep.com.cn/fcse/EN/10.1007/s11705-017-1658-7
https://academic.hep.com.cn/fcse/EN/Y2017/V11/I4/516

Fig.1 The diagram of GIS

Fig.2 Drug concentration-time profiles of ketoconazole in the (A) gastric, (B) duodenal, and (C) jejunal chambers in GIS. Circles represent observed drug concentration and black lines indicate the theoretical concentration curves. Each data point represents mean±SD (n = 4)

Fig.3 Drug% dissolved-time profiles of a tablet of 200 mg ketoconazole in the sum of duodenal and jejunal chambers in the GIS, 50 mL of 10⁻² N HCl (pH 2.0) with 250 mL of water, and 300 mL of 50 mmol/L phosphate buffer (pH 6.5). and the USP apparatus II at pH 6.5 50 mmol/L phosphate buffer (pH 6.5). Black and red circles are representing the dissolution profiles of ketoconazole in the GIS and USP II, respectively. Dots represent the mean of observed values and lines represent the calculated non-linear curves fitting on the observed values. Each data point represents mean±SD (n = 4)

Tab.1 Chemical/physiological/pharmacological parameters of ketoconazole for GastroPlus^TMsimulation

Fig.4 Average plasma ketoconazole concentrations after 200 mg orally in normal subjects. Each data point represents mean. Clinical data was extracted from Huang YC [13]

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