1. How does spray drying’s control of particle characteristics work with new pharmaceutical developments?
The pharmaceutical industry is going through a transformation, so SPX designs our dryers to satisfy the demands of the modern pharmaceutical industry. All the easy soluble drug entities have been discovered and now the researchers must go after the rocks, which are insoluble drug substances. The pharmacist’s processing tool box had to expand to handle the new classes of compounds, so they have developed new, more sophisticated drug delivery technologies. These new technologies require more performance from product particles than just acting as carriers for the drug. Today’s particles are now integral parts of complex delivery systems. For this reason, the particles have to exhibit advanced functional properties so important in today’s drug delivery systems. Spray drying has the ability to make particles with these characteristics.
2. How can spray drying be used to microencapsulate drugs?
Microencapsulation works by formulating with multiple ingredients with varied solubility and can be applied to many delivery platforms. For solid dosage, microencapsulation may provide taste masking or controlled release properties. This relates to my earlier comment of the particle having greater importance to the delivery process. Microencapsulation is a cost effective technique to implement the above delivery strategies. The particle is now a functional unit in a larger drug delivery technology.
Spray drying allows particle engineering to develop the particle’s functional characteristics. During spray drying, the feed is atomized forming liquid droplets in the drying chamber. A droplet can only dry from its surface; therefore as the droplet dries, the particle surface becomes enriched with the more soluble ingredient and the less soluble ingredient is left inside the particle. This is how microencapsulation occurs.
3. How will spray drying ability enhance the functional properties of drugs in the future, ie increased bioavailability or sustained release delivery?
The increasing of drug substance bioavailability and implementing a sustained release delivery can be accomplished with spray drying. Pharmacists will formulate two or more ingredients into a solid matrix or dispersion. The solid dispersion increases drug bioavailability by changing its morphology or forming the solid dispersion may also be used to change the drug delivery release of the drug, i.e. controlled or sustained release.
There are two methods to form a solid dispersion, spray drying and spray congealing. For the formulation spray drying method, the pharmacist dissolves the active ingredients with excipients, often polymers, in the spray dryer’s feed. This formulation may be accomplished using aqueous and more often using solvents or even multiple solvent systems. The formulation is then spray dried which is a quick process and locks the solid matrix.
An alternate route to forming a solid dispersion is to form hot melt vs. dissolved solid ingredients. The formulation ingredients must be heat stable to use this technology and the feed delivery system to handle a hot melt is critical in implementing this strategy. The feed is fed into a spray congealer which is a spray dryer like apparatus, but cools the atomized liquid to form solid particles. Instead of heating the atomized droplets evaporating the liquid fraction of the feed as in spray drying, the congealer atomizes the formulation then cools it. As the formulation is cooled, it changes states from the liquid hot melt to a solid. This is called spray congealing. We again are forming a solid matrix which may be used to improve bioavailability or implement a sustained release drug delivery technology.
4. Can the spray drying process be used in parenteral drug delivery?
Spray drying has been used for more than 30 years to process parenteral drugs and is an ideal system for parenteral drugs because it is a closed system. The older parenteral drug applications are used with formulations that are terminally sterilized, which means that the powders are sterilized after processing in the spray dryer. This terminal sterilization may be accomplished using methods like E-beam or autoclaving. The aseptic dryers are equipped with filters on all gas and liquid streams into the processor, CIP and SIP systems. Also the manufacturing suite should be a higher room classification than what would be used for solid dosage processing.
Our customers report producing spray dried powders with less than 1 Colony-Forming Unit (CFU). A low bioburden is vital for this type of processing so the spray dryer feed must be kept free of pyrogens to be successful. The pharmacist should evaluate if this processing is appropriate, recognizing that there may be a drug potency reduction by the use of terminal sterilization technologies. If the potency reduction is significant, the formulation may be aseptically spray dried.
5. Can a spray dryer replace a freeze dryer (Lyophilizer) in parenteral drug processing?
Yes, a spray dryer can replace a freeze dryer in parenteral drug processing for the right applications. Aseptic spray dryers can achieve powders with less than 3% moisture that many parenteral applications require. When manufacturing is combining lyophilization with a sterile milling step, this is an excellent application for aseptic spray drying. Spray drying has excellent control of particle characteristics. Spray dried particles have better flow properties than milled particles because their surface is smooth, not jagged. A patient injected with a spray dried particle may experience less pain than one injected with a milled particle.
Spray drying has many advantages to lyophilization. Aseptic spray drying requires 25% of the manufacturing space and is a faster process that requires less energy and reduced amount of infrastructure and capital equipment. Aseptic spray drying does not require liquid fill line lines or vial loading that lyophilizers have; however it requires aseptic vial powder loading. This loading equipment is readily available from multiple manufacturers. Aseptic spray drying is gaining momentum in applications throughout the world.