Oral pulsed dose drug delivery system

a drug delivery and pulsed dose technology, applied in the direction of biocide, microcapsules, drug compositions, etc., can solve the problems of time-consuming and difficult to optimize drug layering or core making for multiple unit systems, and the timing of sustained release delivery is not suitable, so as to reduce the ph value of the environment, prolong the delay the effect of release time and delay the release tim

Inactive Publication Date: 2010-02-23
SHIRE PLC
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

Benefits of technology

[0047]In one aspect of this embodiment, a semi-permeable polymer, which may comprise a low water-permeable pH-insensitive polymer, is layered onto the outer surface of the enteric layer, in order to obtain prolonged delayed release time. This semi-permeable polymer coating controls the erosion of the pH-sensitive enteric polymer in an alkaline pH environment in which a pH-sensitive polymer will dissolve rapidly. Another pH-sensitive layer may be applied onto the surface of a low water-permeability layer to further delay the release time.
[0048]In ...

Problems solved by technology

However, for certain drugs, sustained release delivery is not suitable and is affected by the following factors:First pass metabolism: Some drugs, such as β blockers, β-estradiol, and salicylamide, undergo extensive first pass metabolism and require fast drug input to saturate metabolizing enzymes in order to minimize pre-systemic metabolism.
These same factors are also problematic in pulsed dose formulations development.
Additionally, drug layering or core making for multiple unit systems is a time-consuming and hard-to-optimize process.
Particularly challenging for formulation scientists has been overcoming two conflicting hurdles for pulsatile formulation development, i.e., lag time and rapid release.
Due to their pH-dependent attributes and the uncertainty of gastric retention time, in-vivo performance as well as ...

Method used

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  • Oral pulsed dose drug delivery system
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  • Oral pulsed dose drug delivery system

Examples

Experimental program
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example 1

Immediate Release Formulation

[0092]The following formulation was used to layer the drug onto sugar spheres. Nonpareil seeds (30 / 35 mesh, Paulaur Corp., NJ), 6.8 kg were put into a FLM-15 fluid bed processor with a 9″ Wurster column and fluidized at 60° C. The suspension of mixed amphetamine salts (MAS) with 1% HPMC E5 Premium (Dow Chemical) as a binder was sprayed onto the seed under suitable conditions. Almost no agglomeration and no fines were observed with a yield of at least 98%. The drug-loaded cores were used to test enteric coatings and sustained release coatings.

[0093]

TABLE 1IngredientsAmount (%)Nonpareil seed88.00mixed amphetamine salts11.40METHOCEL ® E5 Premium0.60Water**removed during processing

[0094]The drug release profile of the drug-loaded pellets of this example is shown in FIG. 3.

example 2

[0095]The following formulation was used to coat the mixed amphetamine salts loaded (MASL) pellets from Example 1 with the EUDRAGIT® L 30D-55 (Rohm Pharma, Germany) coating dispersion. 2 kg of MASL pellets were loaded into a fluid bed processor with a reduced Wurster column equipped with a precision coater (MP 2 / 3, Niro Inc) (see Examples 3 and 4). The coating dispersion was prepared by dispersing Triethyl citrate, Talc and EUDRAGIT® L 30D-55 into water and mixing for at least 30 minutes. Under suitable fluidization conditions, the coating dispersion was sprayed onto the fluidized MASL pellets. The spraying was continued until the targeted coating level was achieved (20 μ) . The coated pellets were dried at 30-35° C. for 5 minutes before stopping the process. The enteric coated PPAMASL pellets were tested at different pH buffers by a USP paddle method. The drug content was analyzed using HPLC. The results showed that the enteric coating delayed the drug release from the coated pell...

example 3

[0098]The following formulation was used to coat the MASL pellets from Example 1 with the EUDRAGIT® 4110D (Rohm Pharma, Germany) coating dispersion. MASL pellets (2 kg) were loaded in a fluid bed processor with a reduced Wurster column (GPGC-15, Glatt). The coating dispersion was prepared by dispersing Triethyl citrate, Talc and EUDRAGIT® 4110D into water and mixing for at least 30 minutes. Under suitable fluidization conditions, the coating dispersion was sprayed onto the fluidized MASL pellets. The spraying was continued until the targeted coating level was achieved. The coated pellets were dried at 30-35° C. for 5 minutes before stopping the process. The enteric coated MASL pellets were tested using a USP paddle method at different pH buffers. The drug content was analyzed using HPLC. The enteric coating delayed the drug release for several hours from the coated pellets until the pH value reached 6.8 or higher, as shown below in Table 3. (Reference #AR98125-3)

[0099]

...

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Abstract

A multiple pulsed dose drug delivery system for pharmaceutically active amphetamine salts, comprising an immediate-release component and an enteric delayed-release component wherein (1) the enteric release coating has a defined minimum thickness and/or (2) there is a protective layer between the pharmaceutically active amphetamine salt and the enteric release coating and/or (3) there is a protective layer over the enteric release coating. The product can be composed of either one or a number of beads in a dosage form, including either capsule, tablet, or sachet method for administering the beads.

Description

[0001]This application is a 371 of PCT / US99 / 24554 filed Oct. 20, 1999, which is continuation-in-part of application Ser. No. 09 / 176,542, filed Oct. 21, 1998, now U.S. Pat. No. 6,322,819 the contents of which are incorporated herein by reference.[0002]This invention pertains to a multiple dosage form delivery system comprising one or more amphetamine salts for administering the amphetamine salts to a recipient.BACKGROUND OF THE INVENTION[0003]Traditionally, drug delivery systems have focused on constant / sustained drug output with the objective of minimizing peaks and valleys of drug concentrations in the body to optimize drug efficacy and to reduce adverse effects. A reduced dosing frequency and improved patient compliance can also be expected for the controlled / sustained release drug delivery systems, compared to immediate release preparations. However, for certain drugs, sustained release delivery is not suitable and is affected by the following factors:[0004]First pass metabolism:...

Claims

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Application Information

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IPC IPC(8): A61K9/48A61K31/135A61K9/24A61K9/26A61K9/28A61K9/22A61K9/32A61K9/50A61K9/52A61K9/54A61K9/58A61K31/137A61K47/26A61K47/38A61P25/28
CPCA61K9/5026A61K9/5047A61K9/5078A61K31/137A61P25/00A61P25/28
Inventor BURNSIDE, BETH A.GUO, XIAODIFISKE, KIMBERLYCOUCH, RICHARD A.TREACY, DONALD J.CHANG, RONG-KUNRUDNIC, EDWARD M.MCGUINNESS, CHARLOTTE M.
Owner SHIRE PLC
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