LYOPHILIZATION TECHNIQUE: OVERVIEW

CONTENT Introduction Advantage Disadvantage Lyophilization cycle Lyophilization equipment Lyophilization container requirement Process to Produce a product that “Love Dry State” Typical Lyophilization Process Design of Lyofreezer Excipients used in Lyophilized Formulation Annealing Applications of Lyophilization Technology Conclusion References

INTRODUCTION Lyophilization means freeze drying. The term “lyophilization” describes a process to produce a product that “loves the dry state”. This process comprises three steps: freezing, primary drying, and secondary drying. The most common form of sterile parenteral powder is freeze dried or lyophilized powder.

ADVANTAGE:- Economic Safe Good stability Long shelf life High activity rate Low moisture Rapid rehydration

DISADVANTAGES:– More complicated development. More expensive manufacturing Specialized capabilities required increased handling and processing time. Volatile compounds may be removed by vacuum.

LYOPHILIZATION CYCLE Step1]:- Sample Preparation Step2]:- Freezing Step3]:- Primary drying Step4]:- Secondary drying Step5]:- Final Product

LYOPHILIZATION EQUIPMENT:- There are essentially three categories of freeze dryers: Manifold freeze-dryer Rotary freeze dryer Tray style freeze-dryer

LYOPHILIZATION CONTAINER REQUIREMENTS Thermal conductivity Minimize the moisture Tight sealing

PROCESS TO PRODUCE A PRODUCT THAT “LOVES DRY STATE” This technique widely used for pharmaceuticals to improve stability and long term storage of labile drugs. Lyophilization or Freeze-drying fills an important need in pharmaceutical manufacturing technology . The most common application of pharmaceutical freeze drying is in the production of injectable dosage forms. This process is also used in the production of diagnostics .

TYPICAL LYOPHILIZATION PROCESS The first step that takes place in lyophilization process is component preparation i.e. the sterile solution should be prepared, compound, mixed, filtered. The filtered solution is filled into containers (vials). Partially insert a special designed rubber closure onto the vials. Aseptically load the vials into a freeze dry chamber. Freeze every single solution in every vial below a pre-determine critical temperature. Using appropriate application of temperature and pressure, sublime the ice from the product.

Powder Solution

DESIGN OF LYOFREEZER Fig: Lyofreezer

The Essential Components of lyofreezer include:- Chamber Shelves Process condenser Shelf fluid system Refrigeration system Vaccum system Sensors Control system

EXCIPIENTS USED IN LYOPHILIZED FORMULATION The design of a lyophilized formulation is dependent on the requirements of the active pharmaceutical ingredient (API) and intended route of administration. A formulation may consist of one or more excipients that perform one or more functions. Excipients for lyophilization usually fit one of the following categories: 1] Bulking agents 2] Stabilizers 3] Buffering agents 4] Tonicity modifiers, surface-active agents 5] Collapse temperature modifiers 6] Antimicrobial product

Annealing Annealing is an additional step involved in freeze drying process which will help to accelerate primary drying. This process involve holding the product at a temperature for defind period. Annealing reduced primary drying rate.

APPLICATIONS OF LYOPHILIZATION TECHNOLOGY Industrial applications: 1] Pharmaceutical industry: 2] Food industry: 3] Other industries:

CONCLUSION Lyophilization (freeze-drying) is often used to prepare dry pharmaceutical formulations to achieve commercially viable shelf lives. The process comprises three steps: freezing, primary drying, and secondary drying. Under appropriate lyophilization conditions, the ice is removed by sublimation during primary drying. Residual water in the freeze concentrate is removed in the secondary drying step. The knowledge of how to control, or at least manipulate, the freezing step will help to develop more efficient lyophilization cycles and biopharmaceutical products with an improved stability.

REFERENCES Akers MJ, Fites AL, Robinson RL. Types of parenteral administration. Journal of parenteral science and Technology, 1987, 41, 88-95. Lapincolt, Williams K. Remington, The Science & practice of pharmacy, Parenteral Preparation, 20th ed, ISE publication, Phelabelphia. 2000, 1, 804-819. S.L. Nail, “The Effect of Chamber Pressure on HeatTransfer in the Freeze Drying of Parenteral Solutions,” PDA J. Pharm. Sci. Technol. 34,358–368 (1980). M.J. Pikal et al., “Physical Chemistry of Freeze-Drying: Measurement of Sublimation Rates for Frozen Aqueous Solutions by a Microbalance Technique,” J. Pharm. Sci. 72, 635–650 (1983).

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