« LIPIDS
fulfi l industrial and consumer needs by enabling simpler formulation handling and processing using conventional (and thus more economic) equipment to produce convenient unit dosage forms such as tablets and powder-fi lled capsules [12, 18-20].
Interestingly, the interplay in surface charges between lipid droplets, silica nanoparticles and ionizable drug molecules is exploitable to improve drug loading effi ciency. This was demonstrated for a weak base molecule, albendazole, which has a pH-dependent solubility and is practically insoluble in most pharmaceutical solvents at neutral pH (Figure 2). Initial acidifi cation of lipids with hydrochloric acid enhanced albendazole solubility to ~40mg/g; subsequent electrostatic adsorption of the free drug molecules (in its cationic form) onto anionic silica nanoparticle adlayers eff ectively aff orded a 6-fold higher, supersaturated loading level in the dry hybrid formulation [21]. Such an electrostatic approach has also been applied in another study to enhance molecular interaction between lipid droplets and silica nanoparticles, where triglyceride emulsion droplets were made positively charged by incorporating oleylamine as an emulsifi er. The formation of electrostatic attraction with the anionic silica nanoparticles allowed the use of signifi cantly lower mass of solid carriers for lipid encapsulation while minimizing material loss during processing under strong mechanical forces [10].
Nanostructure Eff ects on Drug Dissolution and Lipid Carrier Digestion
An important consideration in attempts to “solidify” lipid-based formulations is whether their drug release or solubilization performance from the solid state could be at least as preserved as in the original liquid state. When a solid carrier (such as silica particles) is acting fully “inert” and not impeding the diff usion of the embedded lipid colloids and drug molecules, fast and complete drug dissolution (or release) could be achieved from the solid state for application in immediate- release or fast-acting formulations (Figure 3). The effi ciency of formulation hydration (or dispersion) and release tend to decrease with increasing carrier particle sizes (hence reduced specifi c surface area) and pore lengths [22, 23].
For digestible lipid-based formulations, integrating nanoparticles adlayers or
www.americanpharmaceuticalreview.com | | 11
nanostructures into lipid droplets may provide eff ective control over their enzymatic digestion kinetics, which off er merits in manipulating drug solubilization or precipitation in the gastrointestinal environment [11, 25]. Hybrid silica-lipid particles designed with diff erent internal nanostructures have been shown to enhance the rate of lipid digestion in comparison with dispersed coarse oil droplets (Figure 4). The enhancement in lipid digestibility is predominantly related to the specifi c surface area of the silica nanostructured network. The
Near-Infrared Spectroscopy — A PAT Tool from Raw Material ID to Integrated Process Applications
NIR is widely used in the pharmaceutical industry as a Process Analytical Technology (PAT) tool. The ability of NIR to sample in-, on- or at-line allows each customer to set up the ideal monitoring protocol. Hear how Pfizer has implemented intelligent control and real time optimization of a multi-step drying process.
This webinar examines:
• Pfizer Global Supply’s experience with online NIR systems for integrated process applications: Detailed method validation & FDA approval
• Raw Material Identification - Qualification of products prior to use in production
• Cascading Library for easy method development and validation
• Content uniformity of tablets and capsules using dedicated NIR lab systems
View On-Demand at:
www.americanpharmaceuticalreview.com/metrohmwebinar
Speakers:
Denise Root Metrohm USA
Sponsored by: Dr. Ke Hong Pfizer Global Supply
»
On-Demand Anytime!
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