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Erratum published on 25 November 2020, see Pharmaceutics 2020, 12(12), 1137.
Article

Application of the Gastrointestinal Simulator (GIS) Coupled with In Silico Modeling to Measure the Impact of Coca-Cola® on the Luminal and Systemic Behavior of Loratadine (BCS Class 2b)

1
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065, USA
2
Department of Pharmaceutical and Pharmacological Sciences, Faculty of Pharmaceutical Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
3
Department Engineering Pharmacy Section, Miguel Hernandez University, San Juan de Alicante, 03550 Alicante, Spain
4
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA
*
Author to whom correspondence should be addressed.
Bart Hens & Marival Bermejo should both be considered as a joint first author.
Pharmaceutics 2020, 12(6), 566; https://doi.org/10.3390/pharmaceutics12060566
Received: 19 May 2020 / Revised: 4 June 2020 / Accepted: 16 June 2020 / Published: 18 June 2020
(This article belongs to the Special Issue Mechanistic In Vitro and In Silico Modeling of Oral Drug Absorption)
In the present work, we explored if Coca-Cola® had a beneficial impact on the systemic outcome of the weakly basic drug loratadine (Wal-itin®, immediate-release formulation, 10 mg, generic drug product). To map the contribution of underlying physiological variables that may positively impact the intestinal absorption of loratadine, a multi-compartmental and dynamic dissolution device was built, namely the Gastrointestinal Simulator (GIS). The luminal behavior of one immediate-release (IR) tablet of 10 mg of loratadine was tested under four different fasted state test conditions in the GIS: (i) with 250 mL of water and applying a predetermined gastric half-life (t1/2,G) of 15 min; (ii) with 250 mL of water and applying a t1/2,G of 30 min; (iii) with 250 mL of Coca-Cola® and a t1/2,G of 15 min; (iv) with 250 mL of Coca-Cola® and a t1/2,G of 30 min. After initiating the experiments, solution concentrations and solubility were measured in the withdrawn samples, and pH was monitored. To address the impact of the present CO2 in Coca-Cola® on the disintegration time of the tablet, additional disintegration experiments were performed in a single-vessel applying tap water and sparkling water as dissolution media. These experiments demonstrated the faster disintegration of the tablet in the presence of sparkling water, as the present CO2 facilitates the release of the drug. The buffer capacity of Coca-Cola® in the presence of FaSSGF was 4-fold higher than the buffer capacity of tap water in the presence of FaSSGF. After performing the in vitro experiments, the obtained results were used as input for a two-compartmental pharmacokinetic (PK) modeling approach to predict the systemic concentrations. These simulations pointed out that (i) the present CO2 in Coca-Cola® is responsible for the enhancement in drug release and dissolution and that (ii) a delay in gastric emptying rate will sustain the supersaturated concentrations of loratadine in the intestinal regions of the GI tract, resulting in an enhanced driving force for intestinal absorption. Therefore, co-administration of loratadine with Coca-Cola® will highly likely result in an increased systemic exposure compared to co-administration of loratadine with tap water. The mechanistic insights that were obtained from this work will serve as a scientific basis to evaluate the impact of Coca-Cola® on the systemic exposure of weakly basic drugs for patients on acid-reducing agents in future work. View Full-Text
Keywords: biopharmaceutics classification system (BCS), low aqueous solubility; oral bioavailability; oral drug absorption; in silico modeling; biopredictive dissolution testing; physiologically-based biopharmaceutics modeling (PBBM) biopharmaceutics classification system (BCS), low aqueous solubility; oral bioavailability; oral drug absorption; in silico modeling; biopredictive dissolution testing; physiologically-based biopharmaceutics modeling (PBBM)
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    Doi: 10.5281/zenodo.3833818
MDPI and ACS Style

Hens, B.; Bermejo, M.; Augustijns, P.; Cristofoletti, R.; Amidon, G.E.; Amidon, G.L. Application of the Gastrointestinal Simulator (GIS) Coupled with In Silico Modeling to Measure the Impact of Coca-Cola® on the Luminal and Systemic Behavior of Loratadine (BCS Class 2b). Pharmaceutics 2020, 12, 566. https://doi.org/10.3390/pharmaceutics12060566

AMA Style

Hens B, Bermejo M, Augustijns P, Cristofoletti R, Amidon GE, Amidon GL. Application of the Gastrointestinal Simulator (GIS) Coupled with In Silico Modeling to Measure the Impact of Coca-Cola® on the Luminal and Systemic Behavior of Loratadine (BCS Class 2b). Pharmaceutics. 2020; 12(6):566. https://doi.org/10.3390/pharmaceutics12060566

Chicago/Turabian Style

Hens, Bart, Marival Bermejo, Patrick Augustijns, Rodrigo Cristofoletti, Gregory E. Amidon, and Gordon L. Amidon. 2020. "Application of the Gastrointestinal Simulator (GIS) Coupled with In Silico Modeling to Measure the Impact of Coca-Cola® on the Luminal and Systemic Behavior of Loratadine (BCS Class 2b)" Pharmaceutics 12, no. 6: 566. https://doi.org/10.3390/pharmaceutics12060566

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