Methods for Superdisintegrant-Based Composite Particles for Dispersion and Dissolution of Active Pharmaceutical Agents

Patent metadata

Field	Value
Publication number	US-2016346209-A1
Application number	US-201615235397-A
Country	US
Kind code	A1
Filing date	Aug 12, 2016
Priority date	Apr 16, 2012
Publication date	Dec 1, 2016
Grant date	—

Abstract

The present disclosure provides improved systems and methods utilizing colloidal/ultrafine superdisintegrant-based composite particles for dispersion and/or dissolution of active pharmaceutical agents. In general, the present disclosure utilizes a surfactant-free or near surfactant-free formulation by incorporating a wet milled SDI as a dispersant in the formulation. As such, the present disclosure provides for the preparation of surfactant-free or substantially surfactant-free formulations (e.g., nano-composite micro-particle formulations) by incorporating a wet-milled superdisintegrant (SDI) as the dispersant in the formulations. The advantageous SDI particles (e.g., colloidal/ultrafine SDI particles) of the present disclosure can be used to break-up the aggregates (e.g., nanoparticle aggregates) of the active agents (e.g. poorly water-soluble drugs) in the formulations (e.g., micro-particle formulations) and enhance the recovery of the nanoparticles of active agents during aqueous re-dispersion and their dissolution rate in vitro and in vivo.

First claim

1 . A method for fabricating colloidal and ultrafine superdisintegrant (SDI) particles comprising:
providing SDI particles; wet-milling the SDI particles in a wet media mill to form colloidal and ultrafine SDI particles; wherein the wet-milled SDI particles have a particle size of less than about 5 microns.

2 . The method of claim 1 , wherein the wet-milled SDI micro-particles have a particle size of about 50 nm to about 1000 nm.

3 . The method of claim 1 , further comprising the step of adding the wet-milled SDI micro-particles to active agent particles.

4 . The method of claim 3 , wherein the wet-milled SDI micro-particles are mixed with the active agent particles to form a suspension.

5 . The method of claim 4 , further comprising the steps of: (i) drying the suspension to form a composite of SDI and active agent particles, and (ii) incorporating the dried composite into a solid dosage form.

6 . The method of claim 4 , further comprising coating and drying the suspension onto an excipient via a fluidized bed processor to form a composite of SDI and active agent particles on at least a portion of the excipient.

7 . The method of claim 6 , wherein the drying method is selected from the group consisting of a fluidized bed coating and drying operation, spray-drying, freeze-drying, vacuum drying and oven drying.

8 . The method of claim 4 , wherein a steric stabilizer is used to impart stability to the mixed suspension.

9 . The method of claim 8 , wherein the steric stabilizer is a soluble biopolymer.

10 . The method of claim 3 , wherein at least a portion of the active agent particles are in powder form.

11 . The method of claim 1 , wherein prior to wet-milling the SDI particles, the SDI particles are provided in a suspension at a weight/weight (w/w) % of from about 0.5 w/w % to about 5.0 w/w % with respect to the weight of the water or suspension.

12 . The method of claim 1 , wherein the wet media mill includes milling media, the milling media having a particle size of about 25 μm to about 4 mm.

13 . The method of claim 1 , wherein the SDI particles function to improve tablet dissolution by changing the nature of the drug.

14 . The method of claim 1 , wherein the SDI particles function to improve tablet dissolution by promoting wettability.

15 . The method of claim 1 , further comprising providing active agent particles and wherein the SDI particles and active agent particles are co-wet-milled in size reduction equipment.

16 . The method of claim 15 , wherein the size reduction equipment is selected from the group consisting of a wet stirred media mill, a wet ball mill, a planetary mill, and milling equipment utilizing a high pressure homogenizer.

17 . The method of claim 15 , wherein prior to wet-milling the SDI particles and active agent particles, the active agent particles are provided in a suspension at a weight/weight (w/w) % of from about 5 w/w % to about 40 w/w % with respect to the weight of the water or suspension.

18 . The method of claim 1 , wherein the SDI particles include particles selected from the group consisting of croscarmellose sodium particles, sodium starch glycolate particles, crosslinked polyvinyl pyrrolidone particles, anionic SDI particles, neutral SDI particles and combinations thereof.

Assignees

• New Jersey Inst Technology

Inventors

• Bilgili Ecevit
• Dave Rajesh
• Bhakay Anagha
• Azad Mohammad

Classifications

• A61J3/00

  Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms · CPC title

• A61K9/5161

  Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin · CPC title

• A61K31/216

  of acids having aromatic rings, e.g. benactizyne, clofibrate · CPC title

• A61K9/5138

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• B82Y40/00

  Manufacture or treatment of nanostructures · CPC title