Piramal Pharma Solutions has added a closed-loop spray drying suite to its dedicated peptide facility in Turbhe, India, with Band 5 containment, ISO Class 8 cleanliness, and a feed rate up to 1 litre per hour. The suite can dry highly concentrated solutions with up to 30% water content, targeting…
Piramal Pharma Solutions PPS , the contract development and manufacturing organisation CDMO arm of Piramal Pharma Ltd., has expanded its dedicated peptide development and manufacturing facility in Turbhe, India, with a spray drying suite designed for small-volume, high-potency batches. The suite is a newly added capability at the existing Turbhe peptide site. It converts liquid formulations into dry powders in a single step, and it is built to contain potent compounds and organic solvents up to Band 5, the most stringent tier of the five-band occupational exposure scale used in pharmaceutical manufacturing.
The processing area maintains ISO Class 8 Class 100,000 cleanliness standards. The drying unit accepts a feed rate of up to 1 litre per hour, and PPS states that it can spray dry highly concentrated solutions with up to 30% water content, a capability the company describes as particularly valuable for biomolecules and large peptides. Under optimal conditions, the same unit can also handle low-volume small-molecule formulations. PPS frames the investment as a response to formulation challenges for peptides and other complex molecules, and to growing demand for those molecules.
Peptides are unstable at high temperatures, often require strict control over particle properties, and have few gentle routes from solution to stable solid form. "Peptides present some of the most intricate formulation challenges in pharmaceutical development, owing to their inherent instability and sensitivity to processing conditions," said Dr. Jordi Bacardit, Global Technical Lead on Peptides and Member of the Science Collective at PPS.
A CDMO earns its role by carrying a molecule through the steps a sponsor cannot easily perform in-house: process development, formulation, analytical characterization, and eventually GMP manufacturing. The Turbhe expansion is capacity added ahead of confirmed programmes, on the expectation that peptide projects in development will need formulation services before they need production volume. For sponsors, the existence of a dedicated peptide facility matters because the equipment, the cleaning procedures, and the operating staff are configured around peptide behaviour rather than adapted from small-molecule or biological operations.
The spray drying suite operates as a closed loop with its own inert gas supply, specialised HVAC, airlocked entries and exits, operator isolation, and a dedicated cleaning area. Each element answers a distinct risk. The inert gas loop excludes oxygen, which protects oxidation-sensitive molecules and prevents the flammable atmospheres that organic solvent vapors can form in ordinary air. The airlocks and operator isolation keep personnel away from the product path, and the dedicated cleaning area gives the facility a contained method for changing over between campaigns, a genuine constraint when highly potent material must be removed from equipment without exposing anyone to it.
Inert gas systems of this kind keep the product path at a slight positive pressure relative to the surrounding room, so a leak in the loop pushes gas outward rather than drawing room air inward. Oxygen sensors monitor the recirculating atmosphere, and solvent that evaporates from the droplets leaves the dryer with the exhaust stream, where it can be condensed or scrubbed before the gas returns to the loop. The engineering is more expensive than an open, air-swept dryer, which is why closed-loop processing is normally reserved for programmes that combine potent compounds, organic solvents, or oxygen-sensitive molecules. The Turbhe suite was specified with all three.
Containment up to Band 5 is the central safety specification. Occupational exposure bands classify compounds by potency, typically when a formal occupational exposure limit has not been established, and Band 5 is the most stringent tier, the ceiling of the scale. It is applied to highly potent active ingredients and to processes that release hazardous organic solvents. Because the process is enclosed, solvent vapors are captured within the recirculating gas rather than released into the workspace, and the drug substance never meets room air.
That changes what ISO Class 8 means here. The room rating is a controlled, not aseptic, classification, and it is not the primary contamination barrier. The closed line, the inert atmosphere, and the high-efficiency air handling carry that burden, which is the appropriate arrangement for a product path that is never exposed to the surrounding environment. Product protection and operator protection are different obligations. ISO Class 8 sets a limit on airborne particles in the room; it is a measure of environmental cleanliness for the process. Band 5 containment sets a limit on what may escape the equipment; it is a measure of safety for the people around the process. The two requirements meet in a design where the closed loop is the primary barrier, the room is a secondary barrier, and operators are separated from both.
The equipment is deliberately modest in scale. A maximum feed rate of 1 litre per hour places the unit in the development and early clinical supply range, not in commercial mass production. That is a functional choice for peptides. Peptide active ingredients are expensive, early-stage batch sizes are small, and a small dryer lets formulators screen drying conditions with grams of material rather than kilograms. It also lets the operator move between programmes with less material lost to commissioning each new campaign. The stated figures describe the edges of the operating envelope, not a routine production rate.
Small scale also shortens development cycles. A process development team can run a designed set of experiments on a litre-scale dryer in days, mapping the relationship between inlet temperature, feed rate, atomising gas flow, and outlet humidity, then carry the resulting operating window forward to later scale. On a production-scale dryer the same experiments would consume kilogram quantities of an active ingredient that may exist only in gram quantities at the time the work is done.
Peptides degrade through specific, well-mapped chemistry. In solution, deamidation attacks asparagine and glutamine side chains, oxidation targets methionine, cysteine, tryptophan, and histidine, and hydrolysis can cleave the backbone itself, with bonds such as aspartic acid-proline particularly vulnerable under acidic conditions. Water is the medium for most of this chemistry, oxygen supplies the oxidant, and heat accelerates both the chemical reactions and the physical processes of unfolding and aggregation. The formulation question for any peptide is how to remove the water without adding destructive heat, and how to do it without destroying the particle properties the final product needs.
Spray drying answers that question in one pass. The liquid feed is atomized into fine droplets, and a controlled gas stream evaporates the solvent to leave a powder. The operation takes seconds rather than hours or days. During the constant-rate drying phase, evaporative cooling holds each droplet near the wet-bulb temperature of the gas, which sits well below the dry-bulb temperature of the inlet stream. A heat-sensitive peptide can therefore pass through a process whose inlet gas is far hotter than the molecule could tolerate if the same heat were applied to solution in bulk. As the droplet shrinks and becomes a particle, the remaining water must diffuse from the interior to the surface, the drying rate falls, and the particle temperature climbs toward the outlet temperature. For a heat-sensitive peptide the outlet temperature is often the binding constraint, and a formulation scientist reads the inlet and outlet temperatures together rather than treating either one as the drying temperature. Temperature and solvent environment can be adjusted independently, which is the heart of the method's value. "Spray drying addresses these distinct challenges by allowing tight control over key components like temperature and solvent environment," Dr. Bacardit said.
Particle engineering is the second benefit, and it follows from the physics of droplet drying. Atomizer design, feed concentration, and gas conditions set the droplet size distribution, and the drying kinetics decide what each droplet becomes. If the surface dries and forms a shell early, the particle can inflate into a hollow sphere; if the shell stays pliable, it can collapse or buckle. The outcome ranges from dense particles to low-density hollow ones, with direct consequences for surface area, flow, and dissolution. Spray drying can produce particles with precise and reproducible size, and in some cases amorphous forms with improved dissolution behaviour. That is the mechanism behind the claim that spray drying can enhance bioavailability: a peptide rendered as a high-surface-area or amorphous particle can dissolve faster and more completely.
Water is the hardest common solvent to evaporate in a spray dryer. Its latent heat of vaporization is roughly 2,260 kilojoules per kilogram, about 2.7 times that of ethanol and more than four times that of acetone, and it evaporates more slowly than most organic solvents at comparable temperatures. A feed that is rich in water therefore loads the equipment: more energy to drive the phase change, more gas volume to carry the moisture away, or a slower feed rate. Many drying processes avoid that load by pushing feeds toward low water content or heavy organic cosolvent loads, making evaporation easier but forcing the molecule into a chemical environment it may not tolerate.
The combination also explains the rest of the design. Handling feeds that are partly aqueous and partly organic, loaded with potent solutes, demands the exact configuration that Turbhe has: a closed loop, an inert gas supply, and containment up to Band 5. The three specifications form one system for drying small volumes of highly potent, solvent-bearing, oxygen-sensitive material without exposing the molecule to conditions that degrade it or the operators to material that harms them. The stated figures are maximums, not routine operating points. Individual campaigns will run below them, depending on the stability, viscosity, and target particle properties of each molecule.
Spray drying is not the only route to a stable peptide solid, and the choice between routes depends on what the final product is for. Lyophilisation is the incumbent method for peptide drug products. It is a batch process measured in days: the solution is frozen, the ice is sublimated under vacuum, and the result is a porous cake that is reconstituted before administration. Lyophilisation is gentle on heat-sensitive molecules, but it offers no control over particle size, produces a cake rather than a free-flowing powder, and is slow and energy-intensive. For a product that will always be an injection, it remains the dominant approach.
The case for spray drying is strongest where the target is a powder with specified physical properties. Respirable powders for inhalation need aerodynamic particle sizes within a narrow band, of the order of a few micrometres. Microparticle and microsphere systems for long-acting injectables need controlled size distributions for consistent release kinetics. Orally disintegrating powders and high drug-load formulations need good flow and rapid dissolution. In each case the atomization step is what sets particle size, and the drying step is what sets the internal structure of the particle. A lyophilisation cycle cannot deliver either. A third route, spray freeze drying, atomizes the liquid into a cryogenic fluid and then lyophilises…
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