It is estimated that at least 40 percent — and possibly as high as 90 percent — of new chemical entities (NCEs) are insufficiently soluble, resulting in low bioavailability and decreased efficacy, according to spray drying services provider, Upperton.1 Spray drying can be an enabling technology when it comes to bioavailability and solubility.
As particle characteristics like size and morphology can be controlled accurately, the resulting solubility and bioavailability characteristics can be influenced in a controlled manner. For example, in API manufacturing, spray drying can create stable crystalline constructs that increase API bioavailability by increasing the solubility of the active ingredient. Spray drying can be used for coating and microencapsulation of a pharma product to not only enhance bioavailability but also to create controlled- or delay-release products.
Although spray drying has been widely established in industrial manufacturing of food and chemicals, it took decades to gain acceptance in the pharmaceutical industry, says Michael Levis, Ph.D., principal scientist, particle technologies at Siegfried Ltd. “The availability of spray drying plants for pharmaceutical use — which are able to handle flammable solvents on a plant scale and comply with the cGMP requirements — were the supposition to transform spray drying from an exotic academic method to a widely applied strategy to make insoluble APIs soluble,” he says.
While industrial spray drying in the food and chemical industry is mostly performed in huge mono plants designed for just one product, the pharmaceutical industry requires multipurpose equipment that can be used flexibly for different APIs. “Contract manufacturers that offer spray drying in their portfolio have made the technology available and accessible to companies that would shrink back from the financial expenditure or lead time to install spray drying equipment they would need for clinical phases or even toxicology studies,” says Levis. Just one-third of respondents to the 2016 Nice Insight Pharmaceutical Equipment Annual Survey use spray drying equipment.2 “Using a contract manufacturer, API substances with poor bioavailability can be tested quickly and relatively cost effectively with the benefit of the operational excellence and knowledge of the service provider.”
According to Levis, the best strategy for improving bioavailability of a poorly soluble API is to isolate it in its amorphous form via spray drying. “The amorphous material is many times more soluble than a crystalline form, thus making the product bioavailable,” he explains. “Polymers have to be added to the spray solution to avoid recrystallization during shelf life, downstream processes or application. Therefore, the best solution is to make an amorphous dispersion within a customized polymer matrix. Spray drying from organic solvents in a closed loop spray dryer promises the best success rate as it opens the widest choice for the combination of API and polymer properties.”
Combining this with competent CROs that develop solutions on a lab scale has enhanced the demand to spray dry amorphous dispersions with the goal of overcoming issues with bioavailability. According to the 2016 Nice Insight CRO Outsourcing Survey, 23 percent of respondents rely on CROs for such bioavailability services.
ASEPTIC VS. TRADITIONAL SPRAY DRYING
One type of spray drying that is gaining more attention for improving bioavailability is aseptic spray drying. Aseptic spray drying uses a hot gas to convert a liquid formulation into a dry powder suitable for parenteral applications without the need for terminal sterilization. The aseptic powder can then be filled into different presentations, such as vials. Currently, it is possible to aseptically spray dry products for up to five days continuously, manufacturing large, kilogram quantities of powder.
Efficiencies can be gained using either traditional or aseptic spray drying by co-processing APIs with solubility enhancers or stabilizers, which may not be possible with lyophilization, says Sam de Costa, stabilization project manager at Nova Laboratories. Consider the dissolution times for monoclonal antibodies (mAbs). Usually, mAbs can take a long time to dissolve, ~ 20 minutes in some instances. de Costa says this can greatly be improved by applying spray drying compared to a lyophilized product (see Figure 1). Nova’s patented aseptic spray drying technology, Aerospheres, manipulates the surface area of the powder spheres to dissolve the product instantly.
“Pharmaceutical spray drying has been well established within the pharma sector for many years, especially in the manufacture of APIs,” says de Costa. “The difference is traditional spray drying is carried out under a low bioburden manufacturing environment whereas aseptic spray drying is done under cGMP sterile conditions. This allows you to manufacture a product to injectable grade, allowing it to be used as a parenteral product.”
“From a technical point of view, there is no difference between spray drying and aseptic spray drying,” says Levis. “However, aseptic spray dryers have to be built and qualified to comply with regulations for aseptic manufacturing. For example, steam sterilization of the equipment is required and aseptic conditions must be applied and documented to avoid any microbiological contamination in the spray drying process.”