Gastro-retentive drug delivery system

a drug delivery system and gastro-retentive technology, applied in the field of gastro-retentive drug delivery systems, can solve the problems of insufficient gastric residence time and the general recognition of the vulnerability of floating drug delivery systems

Inactive Publication Date: 2015-07-23
APET HLDG
View PDF6 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0017]The present invention, in an aspect, provides a solution to the particular problems encountered with many drugs that are absorbed (only / mainly) in the proximal site of small intestine The formulations facilitate absorption of active ingredient into the systemic circulation from only a limited part of the (proximal) intestinal tract for an extended period of time after administration, by enhancing the gastro-rentention or gastric residence time of the delivery system, while continuously releasing active ingredient from the system.
[0018]Surprisingly, the present inventors established that, at least in some cases, the use of oral long acting formulations of the invention allows for effective and treatments, not only with fewer dosages per day, but also with total daily dosages significantly below those suggested in the art.
[0019]In a particularly preferred embodiment of the invention, the floating drug delivery system (FDDS) comprises a coating containing a polymer that swells upon contact with water. An FDDS according to this embodiment has the advantage that it can maintain its buoyancy even when (severely) damaged. The vulnerability of floating drug delivery systems is a generally recognized problem. Damaging of the drug delivery system, such as is often encountered during production, transportation and, especially, during ingestion (e.g. as a result of inadvertent chewing motions by the subject taking the formulation), may easily make the gas-filled compartment accessible to water so as to impair its buoyancy, ultimately resulting in insufficient gastric residence time. A solution to this problem is provided by the present invention, as will be illustrated in the appended examples.
[0022]Furthermore, in contrast to (multi)particulate floating dosage forms, the procedure of manufacturing the floating drug delivery system of the invention is simple and straightforward, and therefore economically attractive, in particular when the particle is filled with air.

Problems solved by technology

The vulnerability of floating drug delivery systems is a generally recognized problem.
Damaging of the drug delivery system, such as is often encountered during production, transportation and, especially, during ingestion (e.g. as a result of inadvertent chewing motions by the subject taking the formulation), may easily make the gas-filled compartment accessible to water so as to impair its buoyancy, ultimately resulting in insufficient gastric residence time.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Gastro-retentive drug delivery system
  • Gastro-retentive drug delivery system
  • Gastro-retentive drug delivery system

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0080]A typical example of a gastro-retentive system can be obtained by coating of an empty gelatine capsule with coating comprising at least one pharmacologically active ingredient.

[0081]In a specific embodiment the gelatine capsule is coated with a suspension containing:[0082]drug (e.g. nicotinamide): 1 to 95% of the solids in the suspension;[0083]polymers and release controlling agents: 5 to 99% of the solids in the suspension.

[0084]The amount of drug that will be sprayed onto the capsule is determined by the desired dose of the drug and the concentration of the drug in the coating. The composition of the drug containing coating layer is determined by the desired release profile. Typical polymers like Hypromellosum 4000 mPa·s., viscosity 2% m / V or Eudragit RL PO can be used whereas plasticizers such as Polyethylenglycolum 6000 or dibutyl phthalate can be used. Other excipients that can be used in the coating suspension are magnesium stearate, talc or mannitol. The coating suspens...

example 2

Dissolution of Nicotinamide from FDDS

Materials

[0088]HPMC (Hypromellosum 4000 mPa·s., viscosity 2% m / V) was obtained from Bufa BV, Uitgeest, The Netherlands. Macrogol 6000 (Polyethylenglycolum 6000) was obtained from Fagron, The Netherlands. Eudragit RL PO (Pharma Polymere, Röhm GmbH) was obtained from Chemische Fabric, Kirschenallee, Darmstadt, Germany. Nicotinamide Ph.Eur.quality was used.

Methods

[0089]A number of different coating dispersions (also referred herein as “suspensions”) were prepared (see Table 1). The required amount of HPMC was weighted to a beaker and then mixed with Ethanol (100 ml). Subsequently, the nicotinamide was added in the amounts indicated below. In parallel, in another beaker Macrogol 6000 was prepared by melting at a temperature not higher than 80° C., after melting, ethanol (50 ml) was added and subsequently the required amount of Eudragit RL PO was added. The cooled solution was mixed with the contents of the first beaker to provide a coating dispersion...

example 3

Development of a 300 mg and a 600 mg Nicotinamide Gradient FDDS

Background

[0096]The concept of an FDDS comprising several layers of distinct composition and distinct amounts of nicotinamide was tested. Also the concept of an FDDs comprising an outer coating layer comprising no nicotinamide was tested.

[0097]The aim of the experiment was to optimize the formulation, especially to prevent an initial release burst and to prolong the period of constant nicotinamide release, preferably over the entire residence time of the FDDS in the stomach. This involved testing of formulations containing outer coatings containing a high percentage of hypromellose and outer coatings containing no nicotinamide as well as formulations containing an inner layer with a high percentage of starch.

Materials & Methods

[0098]Nicotinamide was purchased from Sigma-Aldrich, hypromellose 400 mPa·s from Bufa, Starch 1500 from Colorcon and magnesium stearate from Genfarma by. In all experiments demineralized water was ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
densityaaaaaaaaaa
densityaaaaaaaaaa
residence timeaaaaaaaaaa
Login to view more

Abstract

The invention relates to floating drug delivery systems(FDDS) that provide solutions to the particular problems often encountered with floating drug delivery systems described in the art. On such generally recognized problem is the vulnerability of the systems, especially damage to the gas-filled compartment making it accessible to water so as to impair its buoyancy, ultimately resulting in insufficient gastric residence time. The invention, in an aspect, provides a self-repairing FDDS that maintains its floating capacity after damaging. The floating drug delivery systems of the invention, furthermore,allow for incorporation of high loads of active ingredients. The floating drug delivery systems can be designed in such a way that release of active ingredient from the system occurs entirely independent from the pH of the fluid surrounding the system. Furthermore, the procedure of manufacturing the floating drug delivery system of the invention is simple and straightforward, and therefore economically attractive.

Description

FIELD OF THE INVENTION[0001]The invention relates to the fields of pharmacy and medicine. Among others, it relates to oral gastro-retentive drug delivery systems, in particular floating drug delivery systems, and the uses thereof in therapy.BACKGROUND OF THE INVENTION[0002]Oral administration of drugs is the most preferable way of drug delivery due to the simple and comfortable use and flexibility regarding dose strength and type of formulation. These factors may increase patient compliance. More than 50% of commercial drugs available in the market use oral administration for the delivery. During the last five decades, numerous oral delivery systems have been developed to act as a drug reservoir from which the active substance is released over an extended period of time and at controlled rate of release. However, there is evidence that in vivo drug release of solid oral controlled released dosage form is unpredictable despite its excellent in vitro release profile (Welling, PG 1993)...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/16A61K31/455A61K31/198A61K9/00
CPCA61K9/1652A61K9/0065A61K9/1676A61K31/198A61K9/1635A61K31/455A61K9/1641A61K9/2054A61K9/4891Y10T436/143333A61K9/4808A61P25/00A61P25/14G01N33/6893
Inventor MEIJERINK, HENDRIK JAN CORNELISCHANGOER, LEKHRAMBLOM, WILLEMVISSER, MARINELLA REGINAFRIJLINK, HENDERIK WILLEMEISSENS, ANKO CORNELUS
Owner APET HLDG
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap