From Lab to Pharmacy: The Power of Spray Drying in Drug Development
Welcome back to the “Colorful Researchers” blog. In my first post, I discussed the importance of freeze-drying and the lyophilization process for preservation, using human breast milk as an example. In this post, I would like to discuss my other passion, spray drying, and explain how it is used in drug development.
Spray drying is a versatile and widely used process in the pharmaceutical industry for drug development and formulation. Its application spans from the production of simple bulk powders to the creation of complex drug delivery systems. I learned a lot about how spray drying can enhance the solubility, bioavailability, and delivery of drugs from Bart, and I highly recommend checking out his post on using spray drying to formulate inhalable drugs.
The adaptability and efficiency of spray drying make it an indispensable tool for modern drug formulation strategies, but to maximize the technique and optimize processes, one must understand a few essential concepts.
Traditionally, spray drying has been used to formulate small-molecule drugs with low solubility; however, many improvements and optimizations have made processing larger biomolecules and biopharmaceuticals possible.
What is Spray Drying?
The spray drying technique, developed in 1860, transforms a liquid (solution, suspension, or emulsion) into a dry powder in a single step by atomizing the liquid into a hot gaseous medium. It was originally adopted by the dairy and food industries, mainly for milk production during World War II, to reduce the weight and volume of food and other materials. Over time, the commercialization of spray dryers increased along with the number of spray drying applications across multiple sectors, including pharmaceuticals.
What are the Advantages of Spray Drying?
The method offers numerous advantages, such as consistent powder quality, controllable and continuous processing, and high adaptability. It is suitable for both heat-sensitive and heat-resistant materials. Spray drying is particularly valued in pharmaceutical manufacturing as it is more economical than lyophilization when applicable.
How Can We Optimize the Process for Drug Development?
Drug dissolution and solubility are the most critical parameters in drug development, and the Noyes-Whitney equation is fundamental when utilizing spray-drying techniques to enhance drug delivery systems.
The Noyes-Whitney Equation
- This equation explains the rate of dissolution of solid substances in a solvent. It is given by: dC/dT = kS(Cs-Ct)
- It describes the change in concentration over time (dC/dT) as a function of the dissolution rate constant (k), surface area (S), solubility (Cs), and concentration in the bulk fluid (Ct).
- The following equation is relevant to spray drying for drug development: dC/dT = (kS(Cs-Ct)/L
- whereby (L) represents the thickness of the diffusion boundary layer surrounding the solid.
Its relevance to drug development includes surface area optimization and particle engineering. Spray drying allows for the precise control of particle size and morphology, directly influencing the surface area of the drug particles. A higher surface area increases the dissolution rate, which is particularly beneficial for poorly soluble drugs. By adjusting process parameters, spray drying can produce particles with specific characteristics and porosity, affecting the thickness of the diffusion boundary layer and thereby further optimizing the dissolution rate. By managing the size and distribution of particles, more stable formulations with improved solubility characteristics can be created.
How Can Lipophilic Drugs Be Developed Using Spray Drying? - An Application Example
The word lipophilic comes from the Greek words for “fat” and “friendly.” It refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents. Such compounds differ from hydrophilic (“water-friendly”) substances that tend to dissolve in water and other hydrophilic substances.
Here is an application example that outlines the use of spray drying utilizing BUCHI’s Mini Spray Dryer S-300 in the development of nanoparticles containing RR01, a lipophilic drug, for pharmaceutical and medical applications:
- Sample Preparation: The drug and excipient are prepared in concentrations of 5% w/v. with ratios of 19:1 and 1:1, respectively, using a methanol/water solution. The carrier used is Eudragit L100-55, a poly (methacrylic acid-coethylacrylate), forming a nanoparticle suspension.
- Spray Drying Parameters: Key parameters include an inlet temperature of 50ºC, an outlet temperature range of 37 – 42ºC, a pump rate of 4 ml/min, a gas spray flow of 500 Nl/h, a drying gas flow of 20 m3/h, and a nozzle diameter of 0.5 mm.
- Results: This process achieves particle sizes of 10.9 ± 0.2 microns and 9.9 ± 0.5 microns for drug/polymer ratios of 1:19 and 1:1, respectively, and produces a shriveled surface morphology. The yield was approximately 70%, with an encapsulation efficiency close to 100%.
This application shows the suitability of this method for microencapsulating highly lipophilic and pH-sensitive compounds for oral drug delivery. It is important to remember the significance of process optimization in spray drying for drug development. The given spray drying parameters are a starting point for optimization, which is crucial for determining the feasibility of spray drying a particular material.
Process optimization and understanding equations such as the Noyes-Whitney Equation are vital for achieving the desired particle size, morphology, yield, and encapsulation efficiency, which are critical factors in the effectiveness of the drug delivery system.
By fine-tuning the spray drying process, you can enhance a drug's overall performance, making it more effective for its intended therapeutic use. This was at the forefront of our design decisions when creating the Mini Spray Dryer S-300. Its high levels of precision and adaptability make it the ideal companion to modern, high-efficiency, high-efficacy drug development.
Bueno Chao,
Bruno