Optimization technique

Optimization technique - Parameters and Statistical design method

1. KARPAGAM COLLEGE OF PHARMACY COIMBATORE-32 OPTIMIZATION TECHNIQUE IN PHARMACEUTICAL FORMULATION AND PROCESSING Presented By, Navaneethakrishnan.P Department of Pharmaceutics M.Pharm Semster 1 1 Department of Pharmaceutics

2. 2 Department of Pharmaceutics Contents Introduction Optimization Parameters Statistical Design Evolutionary Method Simplex Method Search Method Karpagam College of Pharmacy, Coimbatore-32

3. 3 Department of Pharmaceutics INTRODUCTION Optimization is a Tool to quantitative a formulation that has been Quantitatively determined. Optimization is not a screening Technique, it is useful in one qualitatively selects a formulation The word “OPTIMIZE” is defined as to make as Perfect or functional as possible. Optimization technique provides a both a depth of understanding and ability to explore and defined a ranges for formulation and processing parameter It helps for the pharmaceutical scientist to understand the theoretical formulation and target processing parameter The term “OPTIMIZATION” is used in pharmacy relative to formulation and processing. Karpagam College of Pharmacy, Coimbatore-32

4. 4 Department of Pharmaceutics Karpagam College of Pharmacy, Coimbatore-32 Optimization Parameters Problem Types Variable Types Constraints Dependent variables Independent variables Unconstraint

5. 5 Department of Pharmaceutics Karpagam College of Pharmacy, Coimbatore-32 Problem Types Constraints: The Constrain optimization problem are restricted one It placed on the system by physical limitation (example Economic restriction) In other hand Constraints problem, one can make hardest tablet but it must disintegration in less than 15 min. Constraints optimization problems only exist because formulators always wish to place restriction in formulation, assume the hardest tablets would posses a low compression and ejection force and faster disintegration and dissolution rate. Unconstraint: In the Unconstraint optimization problem, there is no restriction for a pharmaceutical system. One can prepare most harder tablet as possible. Unconstraint optimization problem is almost not exist.

6. 6 Department of Pharmaceutics Karpagam College of Pharmacy, Coimbatore-32 Variables There are two types in variables Independent Variables: The Independent variables are the formulation and process variables directly under the control of formulation Examples : Dilution ratio, Compression force , Binder and Lubricant Level etc., Dependent Variables: Dependent Variables are the response or the characteristic of the in-progress material or resulting drug delivery system. These are the direct result of any change in formulation. Example : Disintegration time, Hardness, Dissolution rate etc.,

7. 7 Department of Pharmaceutics Karpagam College of Pharmacy, Coimbatore-32 Statistical Design It is widely used for optimization, It may be divided into two general category First type is Evolutionary Operation and Simplex Method Second type is Classic Mathematical and Search Method For the second type is require relation between any independent variables and one or more independent variable be known To obtain a necessary relationship there are two possible approaches the theoretical and the empirical If the formulation knows a theoretical equation for the formulation properties, it does not require a experiment

8. 8 Department of Pharmaceutics Karpagam College of Pharmacy, Coimbatore-32 Evolutionary Operation (EVOP): One of the most widely used methods of experimental optimization in fields other than pharmaceutical technology is evolutionary operation (EVOP). This technique is suited for production situation. The basic production procedure is allowed to evolve the optimum by planning and and constant a repeatation . The process procedure for a products that meets all specifications and generates information on product improvement. By this method experiment makes a very small changes in the formulation and process but it makes it so many times ( i.e repeats the experiment so many times) and the experiment determine the product improvement. In case of the optimum product were obtained then experiment further doesn’t proceed. In industry these process are run over and over again.

9. 9 Department of Pharmaceutics Karpagam College of Pharmacy, Coimbatore-32 Simplex method : Simplex method are used in the analytical methods (a continuous flow analyzer). A simplex is geometric method in which it is represented as triangle based on two factor or independent variables. Once the Simplex has been determined then its successive calculation of comparing a magnitude of response. Example: Two reagent required in the analysis reaction. The initial simplex represented by lowest triangle. Vertices represented by spectrophotometric response. Since the worst response is 0.25 The better response by moving away from the worst response. Optimum response is 0.721

10. 10 Department of Pharmaceutics Karpagam College of Pharmacy, Coimbatore-32

11. 11 Department of Pharmaceutics Karpagam College of Pharmacy, Coimbatore-32 Search method : The search method also applied in pharmaceutical system. It makes a five independent variables into account and it is computer assisted The preson unfamiliar with maths and computer could not carry out a optimisation study Example: In this system also Tablet formulation was selected The five independent variables are selected they are : Diluent ratio Compressional force Nisintegration level Binder level lubricant level

12. 12 Department of Pharmaceutics Karpagam College of Pharmacy, Coimbatore-32 The Dependent variables: Disintegration Time Hardness Dissolution Friability Weight Uniformity Thickness Porosity Mean pore diameter The Experimental design used showed in the table 1. The fact thet there are five independent variables dicates that a total of 27 experiment or formulation be prepared. This design known as a Five factors. The first 16 formulation represent a half factorial design for five factors at two levels, resulting in ½ * 2 5 = 16 trials.

13. 13 Department of Pharmaceutics Karpagam College of Pharmacy, Coimbatore-32 The two levels are represented by +1 and -1 analogue to the high and low values in any two level factorial design.

14. 14 Department of Pharmaceutics Karpagam College of Pharmacy, Coimbatore-32 Steps in Search method: Select a system Select a variable Perform the experiment Submit a data for statistical analysis Set a specifications for feasibility program Select a constraints for grid search Evaluate

15. Department of Pharmaceutics 15 Karpagam College of Pharmacy, Coimbatore-32 Reference: Modern Pharmaceutics by Bankar , Fourth edition Page .No : 607 to 618 . wikipedia.org

16. Department of Pharmaceutics 16 Thank You