Process Development and Scale Up

The availability of a large-scale production method is the prerequisite for the introduction of any product to the market. The term Nanomedicine, as coined by NIH, refers to the application of nanotechnology for treatment, diagnosis, monitoring, and control of biological systems. Nanoparticles, by and far the most exploited products of nanotechnology, are defined as submicron particles having size in nanometer dimensions. Numerous nanoparticle-based drug delivery and drug targeting systems have been developed or are currently under development which include different polymeric and metal nanoparticles, liposomes, micelles, quantum dots, dendrimers, microcapsules, cells, cell ghosts, lipoproteins, and many different nanoassemblies. For pharmaceutical purposes, nanoparticles are solid colloidal particles ranging in size from 10 to 1000 nm (1 μm) and consisting of macromolecular materials in which the active principle (drug or biologically active material) is dissolved, entrapped, encapsulated and/or to which the active principle is adsorbed or attached. Often, the production methods for polymeric nanoparticles are only applicable on lab scale. Large-scale methods are not available, or sometimes the equipment cannot be qualified or does not yield a product of a quality that is acceptable to the regulatory authorities. Further, the production method needs to be low cost to make the nanoparticulate product competitive to conventional dosage forms. If the therapeutic benefit or a new nanoparticulate dosage form is limited, the public health systems could tend to go for the cheaper traditional product. A cost-intensive large-scale production method is no problem if the nanoparticulate product is the only way of treatment or if it is distinctly superior in therapy (e.g. more effective in reducing treatment time, hospitalization time of patients, and subsequently reducing the total treatment costs)”. Further, to summarize the current market status of polymeric nanoparticles they have indicated that, “The major obstacles for the introduction or solid polymeric nanoparticles to the market are the status of excipients (e.g., polymers, toxicity, etc.) and lack of large-scale production methods yielding a product of acceptable quality”. Thus, all these literature reports clearly signify that there is an immense requirement to amend the current set of conditions addressing pharmaceutical nanotechnology and either develop new methods with scale-up capability or design new equipments to tackle the scalability issues encountered with the currently employed methodologies. Literature reports describe different ways to prepare nanopaticles at the laboratory scale, but none of the reports indicate the scalability of these methods. Thus there is a dire need to modify these techniques to achieve the goal of producing tailor-made nanoparticles and at the same time handle the restrictions posed at scale up stages. A few reports indicate the scale up of nanoparticles including systems like inorganic nanoparticles, solid lipid nanoparticles,nanoparticles prepared by using supercritical fluid technology, but no method has been reported for the scale up of nanoparticles of pharmaceutical interest.

We have in the past and are currently working on scale-up and process development of nanosuspensions, polymeric nano particles, nano crystals by attempting to break the barriers restricting 'bench-to-bedside' translation, particularly for nano formulations.