Oral jelly of Metformin hydrochloride formulation development using design of experiments and characterization.pptx

The jelly formulation are easy to carry by users, have ease to self administration without swallowing difficulty and hence improve overall patients compliance. the experimental trial and optimization of oral jelly was carried out by use of DOE statistical method.

1. ORAL JELLY OF MRTFORMIN HYDROCHLORIDE – FORMULATION DEVELOPMENT USING DESIGN OF EXPERIMENTS AND CHARACTERIZATION GRADUATE SCHOOL OF PHARMACY DEPARTMENT OF PHARMACEUTICS PRESENTED BY   JIGNA KHASIYA M.PHARM SEM I GUIDED BY DR. MANJU MISRA ASSOCIATE PROFESSOR 1

2. Impact factor : 3.981 2

3. List of Contents  Introduction Aim   Hypothesis Objective Material and Method Result Conclusion References 3

4. INTRODUCTION : Type-2-diabetes : Type 2 DM is a heterogeneous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion, and increased glucose production. Type 2 diabetes is sometimes called a "life style" disease as it more common in people who don’t do enough exercise, have an unhealthy diet and obese. 4

5. INTRODUCTION :  Metformin hydrochloride is a typical biguanide, chemically known as 3-( diaminomethylidene )-1,1-dimethylguanidine hydrochloride.  Metformin is an oral antihyperglycemic drug used in the management of non-insulin-dependent diabetes mellitus (NIDDM).  It is typically used as pharmaceutically acceptable salt preferably hydrochloride salt.  Metformin hydrochloride is a white to off white crystalline compound with bitter taste having molecular formula C4H11N5 HC1 with molecular wt of 165.63.  It is freely soluble in water and practically insoluble in acetone, ether and chloroform. The jelly formulations are easy to carry by users, have ease of self administration without swallowing difficulty and hence improve overall patient compliance. Considering the advantages as listed above, this work was aimed to develop oral jelly formulation of metformin hydrochloride. 5

6. BASICS OF DOE : Design of experiments (DOE) is defined as a branch of applied statistics that deals with planning, conducting, analyzing, and interpreting controlled tests to evaluate the factors that control the value of a parameter or group of parameters. Design of experiments (DOE)  is a systemic method to determine the relationship between factors affecting a process and the output of the process. Design of experiments (DOE) is a powerful statistical technique for improving product / process design and solving process / production problems. Design of experiments (DOE) is also referred to as Designed Experiments or experimental design.  6

7. WHY DOE : Reduce time to design / develop new products & processes. Improve performance of existing processes. Improve reliability and performance of products. Achieve product & process robustness Perform evolution of materials, design alternatives, setting component and system tolerances. 7

8. FACTORS, LEVELS , RESPONSE : FACTORS : Factors are input to the process Factors can be classified as either controllable or uncontrollable variables. In this case the controllable factors are flour, eggs, sugar and oven. LEVELS : Levels represent settings of each factor in the study. Examples include the oven temperature setting, no. Of spoons of sugar, no. Of cups. RESPONSE : Response is output of the experiment. In the case of cake baking, the taste, consistency, and appearance of the cake are measurable outcomes potentially influenced by the factors and their respective levels.  8

9. HYPOTHESIS : 9

10. AIM & OBJECTIVES : AIM :  To formulate Oral jelly of metformin hydrochloride by using Design of Experiments and characterization. OBJECTIVES : To assess the impact of concentrations of sodium CMC, sucralose and propylene glycol as individual variables on the selected responses to arrive at an optimized formulation, a two level full factorial design with four center points was employed in the study. In-vitro drug dissolution 10

11. Material and Method : Metformin hydrochloride  Sucralose  Propylene glycol  Sodium CMC  Sunset yellow  Mango-orange flavor  Purified water  11

12. EVALUATION OF ORAL JELLY :  12

13. Table 1 : shows the experiments designed using the software for 2 level, 3 factors, full factorial design with 4 center points with respective responses received.  13

14. RESULT : Design of experiments results (responses)   : The results of the experiments randomly chalked out by the Design Expert software are depicted in Table 1.  It can be observed, when sodium CMC concentration was varied from 0.6% w/w to 1.8% w/w, quantity of sucralose was varied from 0.8% w/w to 1.6% w/w and quantity of propylene glycol was varied from 2% w/w to 14% w/w, the resultant viscosities of the formulations were observed in the ranged between 3138 cps and 102519 cps.  The pH of the formulations were found in the range between 6.26 and 6.98. Transparency was scored between 1 and 4. Taste masking score was observed between 1 and 4.  Refractive index was observed to fall in the range between 1.384 and 1.403.  14

15. OPTIMIZATION OF DESIGN SPACE : Table 2.  Significant effects observed for different responses.  15 Note: A =sodium CMC, B =sucralose, C =propylene glycol, AB =Interaction of sodium CMC, sucralose, AC =Interaction of sodium CMC and propylene glycol.  Sr. No.  Responses Significant effects  1. Viscosity  A, AC, C 2. PH  AB, AC, C 3. transparency A,C 4. Taste masking C 5. Refractive index C

16. Result : 16

17. Optimization of design space : Fig. 2. 3 D surface graphs of all responses  indicated in the 3D graph, as concentration of sodium CMC increases from experimental values of 0.6% w/w to 1.8% w/w, the viscosity increases gradually up to 1.2% w/w concentration, but increases rapidly when concentration approaches 1.8% w/w.  17

18. Fig. 2. 3 D surface graphs of all responses.  18 Individual responses were analysed for various statistical parameters provided by Design Expert software. The 3 D graphs for the respective responses are as depicted in Fig. 2. 

19. In-vitro drug dissolution : The optimized formulation after treatment in DOE software was subjected to in vitro release and was compared against metformin hydrochloride tablets procured from Indian market.  The comparative dissolution profiles are shown in Fig. 3. for 1000 mg. For initial time points i.e. 5 min. faster dissolution was seen from jelly compared with tablets. This may be due to dissolved form of drug in jelly whereas tablets require some time to disintegrate.  As observed from the dissolution rate graphs, both marketed formulations and prepared oral jelly of metformin hydrochloride released the drug in faster manner, with dissolution of more than 85% within 15 min indicating the similarity between two release profiles.  19 Fig. 3. Comparative dissolution profile of marketed tablets vs. oral jelly (1000 mg). 

20. Stability of the finished product : Table 5 Stability data of oral jelly 1000 mg/5 g.  20 The stability data indicates that there was no drop in assay of the active at accelerated as well as two long term conditions. The viscosity values were not significantly altered during the stability of the product and there were no significant differences in the dissolution rates at 30 min time interval from initial values during the stability period under evaluation. Thus, the data indicates the quality of the product remains within the specified limits for 6 months. 

21. Conclusion : The prepared formulations of oral jelly were compared with marketed tablets formulations for dissolution profile and the drug release was found to be equivalent. The challenges of solubilization of the drug, taste masking were overcome successfully. The product was found to be stable in ICH stability conditions for Zone IVb (long term condition as 30 ◦C/75%RH).  Design of Experiments concept using Design Expert software was used for optimization of formulation.  The research work was conducted to develop oral jelly of metformin in immediate release form, for ease of swallowing to offer the finished product in the unit dose packaging and the researcher believe that this would make an important step for patient compliance.  21

22. References : N. Bharadwaj, A. Kumar, A. Choudhary, R. Choudhary, R. Bala, A review on immediate release drug delivery system, Int. Res. J. Pharmaceut. Appl. Sci. 4 (1) (2014) 78–87.  M. Gosch Stegemann, J. Breitkreutz, Swallowing dysfunction and dysphagia is an unrecognized challenge for oral drug therapy, Int. J. Pharm. 430 (Issues 1–2) (2012) 197–206.  V. Payot , A.-C. Cordonier , J. Marquis, O. Bugnon , K.E. Hersberger, M.-P. Schneider, I. Arnet, Prevalence of patients’ difficulties in swallowing solid SODF, Int.J . Clin. Pharmacol . 33 (2011) 402.  Optimizing drug delivery systems using systematic "design of experiments." Part I: fundamental aspects, Crit. Rev. Ther. Drug Carrier Syst. 22 (1) (2005) 27–105.  Raymond C. Rowe, et al., Handbook of Pharmaceutical Excipients, Pharmaceutical Press and American Pharmacists Association, 2009.  K. Tandel, Sugar substitutes: health controversy over perceived benefits, J. Pharmacol . Pharmacother . 2 (4) (2011) 236–243.  Product brochure. http://sapphireinstruments.com/PDF/REFRACTO-METER.pdf. (Accessed 27 December 2020).  22

23. Thank you  23