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Novel Method

a technology of paracetamol and formulation, applied in the field of new methods, can solve the problems of delayed absorption of other drugs, serious clinical consequences, etc., and achieve the effects of improving analgesia, reducing intrapatient variability, and improving absorption of active agents

Inactive Publication Date: 2014-03-06
GLAXO SMITHKLINE LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to a method for improving the effectiveness of medications that are not well absorbed in the stomach, such as paracetamol, in patients with gastric dysmotility. The method involves giving the patient a specially formulated medication containing calcium carbonate, a binding agent, and a disintegrating agent. This medication is designed to help reduce the variations in the patient's response to the medication, and can provide better pain relief for diabetics or improve the absorption of the medication in patients with gastric dysmotility.

Problems solved by technology

The importance of dysmotility in patients, particularly the elderly, may result in serious clinical consequences where clinical response to a medication is delayed, such as in delayed levodopa absorption or with diuretics.
As opioids and anticholinergics already have inhibitory effects on gastric emptying, this may delay the absorption of other drugs.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Pharmacokinetic Profile in Gastric Dysmotility Patients

[0052]Long standing diabetes may have reduced gastric motility by up to 50%. Therefore, patients with type 2 diabetes were chosen as a dysmotility model to evaluate the PK profile of paracetamol from two different formulations. This study was a single centre, two way, open label, randomized, single dose, cross over PK study. Subjects received a single 1 gm oral dose of a formulation of the invention or standard paracetamol formulation, 2 hours after a standard meal, with randomly assigned patients having a 24 hour wash out between dosing. 21 patients completed the protocol, 18 males, and 3 females. Blood samples were taken 4 hours post-dose for pharmacokinetic analyses.

[0053]The primary study objective was to compare early exposure, as assessed by rate of absorption (area under the curve [AUC]0-30 mins). Other early exposure variables included time to maximum concentration (Tmax), and inter-patient variability (coefficient of va...

example 2

Pharmacokinetic Parameter Study

[0063]It had previously been determined in a clinical study that the Paracetamol / calcium carbonate containing formulation (as described above) is emptied from the stomach more rapidly than a standard paracetamol (SP) tablet formulation. The study below compares the PK parameters of Paracetamol / calcium carbonate containing formulation and the standard paracetamol tablet, and to assesses their variability, since these can influence analgesic efficacy and response rates.

Methods

[0064]A total of 76 healthy volunteers were recruited in an open-label, randomised, 8-way crossover study. Each formulation was administered in a replicate fashion, with a single 1 g dose taken 2 hours after a standard meal on 4 separate days. Blood samples were taken up to 10 hours after the initial dose and 4 hours after the replicate doses for pharmacokinetic (PK) analysis.

[0065]The primary objectives were: early exposure (rate of absorption, AUC0-30 mins, after both initial and ...

example 3

Disintegration and Gastric Emptying

[0070]Tablet disintegration and dissolution are key factors in in vivo speed of absorption and downstream pharmacokinetic parameters. Using the Paracetamol / calcium carbonate containing formulation an in vivo gamma scintigraphy investigation of tablet disintegration and gastric emptying (GE) was conducted.

Methods

[0071]This single-dose, cross-over study involved 24 healthy volunteers. All participants ate a standard radio-labelled breakfast 2 hours (h) before taking the study medication (1 g paracetamol as either as Paracetamol / calcium carbonate containing formulation (described above) or a standard paracetamol tablet formulation described above (SP) [111indium-DTPA-labelled tablet]).

[0072]The rate of disintegration was measured using gamma scintigraphy after defining the stomach area as the region of interest. Data were analysed using the WebLink® image analysis program. Onset and completion of tablet disintegration were determined by qualitative as...

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PUM

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Abstract

The present invention is directed to a novel method for reducing intrapatient variability in pharmaceutically active agent which is suitably not absorbed in the stomach, such as paracetamol, containing formulations in patients having gastric dysmotility, or a method of improving analgesia in a diabetic patient, or improving absorption of an active agent is a patient with gastric dysmotility, which methods comprises administering orally to said patient in need thereof a pharmaceutical dosage form comprising a first active agent, calcium carbonate, at least one first binding agent, and at least one disintegrating agent as intragranular components in the form of a granulate, and as an extragranular component at least one hydrophilic colloid, an optionally a second binding agent, calcium carbonate, a super disintegrant, and a second active agent.

Description

FIELD OF THE INVENTION[0001]The present invention is directed to novel methods of use for paracetamol containing formulations which deliver rapid dissolution of the active agent followed by improved absorption in patients with delayed gastric emptying.BACKGROUND OF THE INVENTION[0002]The present invention is the use of a paracetamol formulation that has unexpectantly been shown to have improved pharmacokinetic profiles in patients having gastric dysmotility or gastroparesis. Historically, diabetes has been shown to reduce gastric motility (gastroparesis) by up to 50% in patients as compared to non-diabetic individuals.[0003]Involvement of the autonomic nervous system in patient having diabetes mellitus includes gastric enteropathy characterized by gastrointestinal dysmotility. Bassotti, G., Recenti Prog Med. 82: 334-337 (1991). Long-standing diabetes mellitus may reduce gastric emptying in up to 50% of patients. O'Mahony et al., Drugs Aging, 19: 515-527 (2002). The impact of various...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K47/02A61K31/167
CPCA61K31/167A61K47/02A61K9/2077A61K45/06A61P1/00A61P25/04A61P29/00A61K2300/00
Inventor CLARKE, GEOFFREY DOUGLASGRATTAN, TIMOTHY JAMESBURNETT, IAN
Owner GLAXO SMITHKLINE LLC
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