Nanoparticle Formation: A Modular High Pressure System to Enhance Biopharmaceutical Properties of Poorly Soluble Drugs - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Nanoparticle Formation: A Modular High Pressure System to Enhance Biopharmaceutical Properties of Poorly Soluble Drugs


Pharmaceutical Technology


Pharmaceutical research and development scientists have applied combinatorial chemistry and molecular modeling techniques to develop drug compounds with properties more closely resembling natural mediators in the body. Many of these natural mediators are hydrophobic substances and are synthesized at or near the site of action; thus they do not need to overcome the absorption, distribution, metabolism, and excretion issues associated with administered drugs. To overcome the challenges of absorption and distribution resulting from hydrophobicity and poor solubility, formulators have developed drug delivery systems such as solid dispersions, microemulsions, self-emulsifying systems, complexation, liposomes, and nanostructured particles created using particle-size reduction and particle-formation techniques.

Nanotechnology in particular has several advantages. The approach improves bioavailability, decreases fed fasted variability, and results in a faster onset of therapeutic action for oral doses. Moreover, supersaturation can be achieved with nanonization using mechanical techniques that do not require conversion from a crystalline to an amorphous state (1, 2).


Figure 1: Scanning electron photomicrographs of (a) unprocessed investigational compound 2 (INV 2) (scale 100 μm) and (b) processed INV 2 (scale 1 μm).
Particle size plays an important role in the dissolution rate of a drug. Studies of poorly soluble drugs have demonstrated that reducing the particle size can increase the rate of dissolution and provide a higher bioavailability (3, 4). The majority of these studies involved a mechanical size reduction to particles larger than 1 μm (5). Kondo et al. reported the bioavailability for HO-221 doubled when the mean particle size was reduced from 4.15 to 0.45 μm (6). These studies demonstrate the potential for substantially enhancing bioavailability by particle-size reduction to the submicron range. Liveridge and Cundy (7) reported the absolute bioavailabilities of a nanoparticle donazol formulation (82.3 10.1%) and an aqueous suspension of conventional donazol particles (5.1 1.9%), which suggest that the nanoparticle dispersion can overcome the dissolution rate–limited bioavailability observed with a conventional suspension of donazol.


Figure 2: Photo of (a) the pilot-scale system and (b) the modular process cell and (c) flow couplings, nozzle, cells, seals, and cell retainer (left to right). Absorption cell (reactors and seals) options include various numbers of reactors to control process duration, various reactor geometric designs and sizes to increase or decrease shear, laminar flow (for delicate emulsions), or turbulent flow (for greater impact and reprocessing). Nozzle options include various geometries and sizes, and flow coupling options allow laminar or turbulent flow to minimize or increase cavitation, respectively.
The current study evaluates the feasibility of nanoparticle formation by modulating, in a controlled manner, cavitation, shear, and impact forces. A technique that individually controls these forces to form stable nanoparticle suspension was evaluated, developed, and shown to provide a higher process intensity and to process a much higher solids concentration (more than 60% w/w) (see Figure 1).


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
70%
Breakthrough designations
4%
Protecting the supply chain
17%
Expedited reviews of drug submissions
2%
More stakeholder involvement
7%
View Results
Eric Langerr Outsourcing Outlook Eric LangerTargeting Different Off-Shore Destinations
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAsymmetric Synthesis Continues to Advance
Jill Wechsler Regulatory Watch Jill Wechsler Data Integrity Key to GMP Compliance
Sean Milmo European Regulatory WatchSean MilmoExtending the Scope of Pharmacovigilance Comes at a Price
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Ebola Outbreak Raises Ethical Issues
Better Comms Means a Fitter Future for Pharma, Part 2: Realizing the Benefits of Unified Communications
Better Comms Means a Fitter Future for Pharma, Part 1: Challenges and Changes
Source: Pharmaceutical Technology,
Click here