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Kelly, Kilian; O'Mahony, Bridget; Lindsay, Blythe; Jones, Tamara L.; Grattan, T. J.; Rostami‐Hodjegan, Amin; Stevens, H. N. E.; Wilson, Clive G.

doi:10.1023/a:1026155822121

Cited by 93 publications

(21 citation statements)

References 11 publications

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“…Another imaging technique, namely γ-scintigraphy, has previously been used to study the disintegration time of Panadol and Panadol Rapid in humans. The study showed that Panadol Rapid disintegrated faster compared to Panadol, which, in turn, was linked to faster uptake of the drug [5]. Similar results were seen in a study using magnetic resonance imaging (MRI) to study the disintegration and transit time of Panadol and Panadol Rapid [8].…”

Section: Introductionsupporting

confidence: 71%

“…However, the actual behavior of an oral dosage form in the environment of the gastro-intestinal tract is not very well elucidated using these conventional methods. Clinical studies can be used to validate the behavior of the dosage form obtained in vitro; however, the characteristics of the gastro-intestinal tract, such as dietary state, gastric emptying rate, motility, and the pH, have all been shown to significantly influence the disintegration, dissolution, and absorption of an orally administered drug [5,6].…”

Section: Introductionmentioning

confidence: 99%

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The Use of Capsule Endoscopy to Determine Tablet Disintegration In Vivo

Blaabjerg

Chen

et al. 2020

Pharmaceutics

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The preferred delivery route for drugs targeted for systemic effect is by oral administration. Following oral administration, a solid dosage form must disintegrate and the drug dissolve, thereafter permeating the intestinal mucosa. Several different in vitro methods are used to investigate these processes, i.e., disintegration tests, dissolution tests, and permeability models. However, the actual behavior of oral dosage forms in the environment of the gastro-intestinal tract is not very well elucidated using these conventional methods. In this study, the use of capsule endoscopy to determine tablet disintegration in vivo was assessed. Panadol and Panadol Rapid (acetaminophen/paracetamol) were used as the test material. The in vivo tablet disintegration behavior in beagle dogs was assessed by the use of capsule endoscopy. The in vitro tablet disintegration behavior was assessed using the European Pharmacopeia (Ph. Eur.) disintegration test. The study showed that the in vivo disintegration times of Panadol and Panadol Rapid were 24.7 and 16.5 min, respectively, when determined by capsule endoscopy, which corresponded to the pharmacokinetic data. By contrast, the in vitro disintegration times of the same formulations were 5.5 and 4.0 min, respectively, when determined by the Ph. Eur. disintegration test. In conclusion, capsule endoscopy can be used to determine the in vivo tablet disintegration behavior. By contrast, the in vitro methods appear to not be predictive of the disintegration behavior in vivo but may be used to rank the order the formulations with respect to disintegration time.

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Section: Introductionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

The Use of Capsule Endoscopy to Determine Tablet Disintegration In Vivo

Blaabjerg

Chen

et al. 2020

Pharmaceutics

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“…The increase in dissolution rate is highly likely a result of turbulence caused by gaseous CO 2 release at the level of the tablet/ dissolution fluid interface, leading to a disruption of the boundary diffusion layer. This was consistent with their proposed hypothesis that the generation of CO 2 , resulting from the reaction of sodium bicarbonate with HCl in the stomach, increases the rate of paracetamol dissolution from Panadol Actifast ® tablets compared to the conventional Panadol ® tablets due to CO 2 release that will stimulate the disintegration of the tablet [43,44].…”

Section: Disintegration Of the Tablet In The Presence And Absence Of supporting

confidence: 89%

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)

et al. 2020

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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.

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“…It should be noted that some disintegration of the tablets would have occurred prior to observation of gastric emptying of the radiolabel since the radiolabel is centralised in the tablet core so some non-labelled disintegrated material will have been released prior to gastric emptying of the radiolabelled product. However, it has been shown that administration of radiolabelled and non-labelled paracetamol tablets (using the same method of radiolabelling as used in this study) have similar disintegration rates (8). Onset of disintegration occurred at 43 min (SD = 18.0) and completion occurred at 63 min (SD = 24.8) post-dosing.…”

Section: Resultsmentioning

confidence: 84%

“…Fast-dissolving tablets have been shown to empty from the stomach more quickly than standard tablets, resulting in earlier appearance of the drug in the plasma (7–9) and most importantly, more rapid pain relief (10). Previous studies using the dual investigative techniques of gamma scintigraphic imaging combined with concurrent pharmacokinetic (PK) assessment have shown that the rate of gastric emptying is directly proportional to the rate of paracetamol absorption (7, 8). Since paracetamol is more soluble in hot water but only sparingly soluble in cold water, it is hypothesised that presenting paracetamol as a hot drink will potentially increase the rate of gastric emptying of the drug as it is already in solution form, negating the requirement for prior disintegration and dissolution of conventional tablets.…”

Section: Introductionmentioning

confidence: 99%

Does a Hot Drink Provide Faster Absorption of Paracetamol Than a Tablet? A Pharmacoscintigraphic Study in Healthy Male Volunteers

et al. 2014

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PurposeTo investigate the hypothesis that paracetamol is absorbed faster from a hot drink than from a standard tablet using simultaneous scintigraphic imaging and pharmacokinetic sampling.MethodsTwenty-five healthy male volunteers received both paracetamol formulations in a randomised manner. The formulation administered in the first treatment arm was radiolabelled to allow scintigraphic monitoring. In both treatment arms, blood samples were taken for assessing paracetamol absorption.ResultsFollowing the hot drink, paracetamol absorption was both significantly faster and greater over the first 60 min post-dose compared with the tablet, as evidenced by the median time to reach t0.25 μg/mL of 4.6 and 23.1 min, respectively, and AUC0-60 of 4668.00 and 1331.17 h*ng/mL, respectively. In addition, tmax was significantly shorter for the hot drink (median time = 1.50 h) compared with the tablet (1.99 h). However, Cmax was significantly greater following the tablet (9,077 ng/mL) compared with the hot drink (8,062 ng/mL). Onset of gastric emptying after the hot drink was significantly faster than after the standard tablet (7.9 versus 54.2 min), as confirmed scintigraphically.ConclusionsCompared with a standard tablet, a hot drink provides faster absorption of paracetamol potentially due to more rapid gastric emptying.

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Cited by 93 publications

References 11 publications

The Use of Capsule Endoscopy to Determine Tablet Disintegration In Vivo

The Use of Capsule Endoscopy to Determine Tablet Disintegration In Vivo

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)

Does a Hot Drink Provide Faster Absorption of Paracetamol Than a Tablet? A Pharmacoscintigraphic Study in Healthy Male Volunteers

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