Comparison of a novel fast-dissolving acetaminophen tablet formulation (FD-APAP) and standard acetaminophen tablets using gamma scintigraphy and pharmacokinetic studies

Wilson, Clive G.; Clarke, Cyril P.; Starkey, Y Y; Clarke, Geoffrey D.

doi:10.3109/03639045.2010.538058

Cited by 19 publications

(25 citation statements)

References 23 publications

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“…For the C max of paracetamol and caffeine, the new formulation and the currently marketed product were bioequivalent in semi-fed state and fasted state, except that in the fasted state paracetamol C max was significantly higher following the new formulation treatment. This is indicative of the food effect on paracetamol absorption which is observed in other PK studies for paracetamol [11,19,20]. However the higher paracetamol C max values observed are within ranges previously observed in clinical studies with paracetamol and are not likely of clinical significance.…”

Section: Discussionsupporting

confidence: 83%

“…The caplet core incorporates alginic acid in addition to calcium carbonate. It is postulated that calcium alginate, formed by the reaction of calcium ions with alginic acid in the acidic environment of the stomach, combine with carbon dioxide generated from calcium carbonate, facilitate the formation of a uniform suspension of fine particles with increased surface area leading to enhanced dissolution [11].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic and Bioequivalence Study Evaluating a New Paracetamol/Caffeine Formulation in Healthy Human Volunteers

Liu¹,

Kotler²,

Sharples³

2011

JBB

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Purpose: Aim of this study was to evaluate the bioequivalence and clinical pharmacokinetics of newly developed paracetamol 500 mg and caffeine 65 mg combination (PANADOL ® EXTRA ADVANCE product), compared with currently marketed conventional paracetamol/caffeine caplet (PANADOL EXTRA ® product) in fasted and semi-fed states.Methods: Thirty subjects were enrolled and all completed this 4-way crossover study. Serial blood samples were collected pre-dose until 10-hours post-dose for each period. Plasma samples were assayed for paracetamol and caffeine concentration using HPLC/MS methods. PK parameters were computed using non-compartmental model. Linear mixed-effect model was used to analyze logarithmically transformed AUC 0-∞ , AUC 0-t and C max as well as AUC 0-30min and AUC 0-60min values . T max was analyzed by signed rank test on within-subject differences. Time to reach minimum therapeutic concentration in plasma of 4 µg/ml (T 4 ) for paracetamol was evaluated. The AEs were also assessed. Ratios of AUC 0-∞ , AUC 0-t , and C max were compared for new formulation vs. PANADOL EXTRA ® in fasted and semi-fed states, and analyzed for bioequivalence as determined by 90% confidence intervals (CI90%). Results:Bioequivalence was established between these two formulations in both fasted and semi-fed states, as the ratios were within 0.8-1.25, except the C max of paracetamol in fasted state. In addition, the new formulation showed significantly greater early absorption (AUC 0-30min and AUC 0-60min ), as well as significantly shorter T max , for both paracetamol and caffeine compared to PANADOL EXTRA ® in fasted and semi-fed states. Based on T 4 , paracetamol absorption was twice as fast for the new formulation as compared to the corresponding conventional caplet in the fasted and fed states. The new formulation was safe and well tolerated. Conclusions:The new Panadol ® Extra Advance formulation is bioequivalent to the currently marketed conventional formulation. Both paracetamol and caffeine are absorbed significantly faster with the new formulation compared to Panadol ® Extra product.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and Bioequivalence Study Evaluating a New Paracetamol/Caffeine Formulation in Healthy Human Volunteers

Liu¹,

Kotler²,

Sharples³

2011

JBB

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“…Based on this principle, the acetaminophen absorption technique was introduced as an alternative technique for measuring GE (discussed in the next section: Acetaminophen Absorption Technique). In the development of a novel fast acting formulation containing paracetamol (FD-APAP), the granulate was labeled by the addition of [ 111 In]-labeled DTPA (Wilson et al, 2011). Because scintigraphy allows a more rapid sampling than taking blood, the effects of small changes in dissolution rate of a drug compound become more evident in gastric scintigraphy compared to the acetaminophen absorption technique (Figure 2).…”

Section: Following the Behavior Of Oral Formulations In The Upper Gi mentioning

confidence: 99%

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

Hens

Corsetti

Spiller

et al. 2017

International Journal of Pharmaceutics

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(2017) Exploring gastrointestinal variables affecting drug and formulation behavior: methodologies, challenges and opportunities. International Journal of Pharmaceutics, 519 (1-2). pp. 79-97. ISSN 1873-3476Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/39960/1/FinalVersion-Revised-FOR_EPRINTS_1_YEAR_EMBARGO_ELSEVIER.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the Creative Commons Attribution Non-commercial No Derivatives licence and may be reused according to the conditions of the licence. For more details see: http://creativecommons.org/licenses/by-nc-nd/2.5/ A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. After oral intake, a drug formulation is challenged by several gastrointestinal (GI) barriers. Complex variables such as pH, GI secretions and GI transit/motility along the GI tract can affect drug release and absorption in a positive or negative way depending on the physicochemical properties of the drug compound (e.g. pH/pKa interplay for ionizable drugs) and/or the formulation characteristics (e.g. pHsensitive coating). In addition, inter-subject variability in characteristics of the GI environment may cause variable drug absorption and systemic drug availability (Riethorst et al., 2015). Determining the median and range for specific GI variables, and understanding how they influence oral drug behavior along the GI tract, will be helpful in the field of drug development. 2The present review provides an overview of different methodologies that can be applied to study physiological variables of the human GI tract and their impact on oral drug absorption in healthy and patient populations. The methodologies have been subdivided into two groups: (i) noninvasive and (ii) invasive methodologies. Although some of the methodologies are more historical than operational, they have been of paramount importance for innovations in drug and formulation development; in addition, they have created the basis for several novel methodologies, leading to an in-depth comprehension of different GI variables: gastric emptying (magnetic resonance imaging (MRI), scintigraphy, acetaminophen absorption technique, ultrasonography, breath test, intraluminal sampling and telemetry), motility (MRI, small intestinal/colonic manometry and telemetry), GI volume changes (MRI and ultrasonography), temperature (telemetry) and GI pH (intraluminal sampling and telemetry). Noninvasive methodologiesa. Scintigraphy Disturbances in the normal movement of food along the GI tract can be associated with abdominal pain, early satiety and nausea. Measurement of GI transit, es...

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“…Formulation A is the second (83.97 ± 4, 05%), followed by formulation B (66.20 ± 3.51%) and formulation C in the end (27.91 ± Th e fastest release of the active drug form from the formulation D can be explained by the contents of the formulation. It contains the so-called OptiZorb® technology, which represents a combination of calcium carbonate and alginic acid, the super-disintegrator related to the fast decomposition [23]. Alginic acid in the aquatic medium, rapidly absorbs water and swells, while calcium carbonate was predicted to react with the acid in the stomach, www.hophonline.org…”

Section: Resultsmentioning

confidence: 99%

Influence of immediate release tablet formulation on dissolution profile of paracetamol

Todorović¹,

Goločorbin-Kon²,

Kermeci³

et al. 2018

Hosp Pharm Int Multi J

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Introduction: Paracetamol is analgesic and antipyretic, which is usually in the form of an immediate release tablet formulations. Therapeutic eff ects in terms of the speed and intensity of the analgesic eff ect is dependent on speed of liberation from formulation. Aim: The aim of this work was to determine and compare dissolution profi les of 4 paracetamol immediate release tablet formulations and to determine infl uence of excipients on kinetic of paracetamol dissolution. Materials and Methods: Dissolution profi les of paracetamol tablets were determined using method with paddles and phosphate buff er pH 6.8 as a medium. Release of paracetamol was followed 60 minutes (using 6 time points). Concentration of paracetamol was measured using UV/Vis spectrophotometric method (243 nm). Dissolution profi les were compared using model-independent method (diff erence factor and similarity factor), statistic method (ANOVA-based method and pair Student's T-test, p<0.05) and model dependent methods (to determinate the release kinetics of paracetamol). Results: All formulations in the fi rst 45 minutes liberated more than 85 % of the labled content. Formulation D, which contained superdesintegrator, released 90% of the content in the fi rst 5 minutes. Though based on values of diff erence and similarity factors formulations are, not signifi cantly diff erent, ANOVA-based method showed that formulation A and B, B and C, as well as formulation B and D do statistically diff er in all 6 time points, meaning they have parallel profi les. The release of paracetamol from formulations A and D is best described by the fi rst order kinetic model, while the release of formulations B and C by the logistic model. Conclusions: The release kinetic of paracetamol is mostly infl uenced by the type of superdisintegrants and lubricants. Formulation with superdisintegrant technology OptiZorb ® demonstrated fastes release rate and thus it is expected to produce the fastest pharmacodynamic eff ect.

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Comparison of a novel fast-dissolving acetaminophen tablet formulation (FD-APAP) and standard acetaminophen tablets using gamma scintigraphy and pharmacokinetic studies

Cited by 19 publications

References 23 publications

Pharmacokinetic and Bioequivalence Study Evaluating a New Paracetamol/Caffeine Formulation in Healthy Human Volunteers

Pharmacokinetic and Bioequivalence Study Evaluating a New Paracetamol/Caffeine Formulation in Healthy Human Volunteers

Exploring gastrointestinal variables affecting drug and formulation behavior: Methodologies, challenges and opportunities

Influence of immediate release tablet formulation on dissolution profile of paracetamol

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