CHAPTER 8 HYDROGEL PLUG FORMULATION AND EVAUATION

Transcription

1 CHAPTER 8 HYDROGEL PLUG FORMULATION AND EVAUATION 8.1 Preparation of erodible tablet plug (Hydrogel Plug) Direct compression method was used to prepare the erodible tablet plug. The compositions of different the erodible tablet plugs used were as shown in Table 8.1. The plug ingredients (Hydroxy propyl methyl cellulose (HPMC), Sodium alginate, Guargum, spray dried lactose) were mixed for 10 minutes. (Usha Yogendra Nayak et al., 2009) Magnesium stearate (1%) was added to the previous mixture and further blended for 5 minutes and compressed using single punch tablet machine. (Cadmach,Machines Ltd Ahmedabad, India).The diameter of the tablet plug was 7mm and the weight at varied between mg.(Mahajan et al.,2010) Formulation with HPMC as hydrogel plug (FP1 to FP4) Hydroxy propyl methyl cellulose (HPMC), spray dried lactose were mixed for 10 minutes.. Magnesium stearate (1%) was added to the previous mixture and further blended for 5 minutes and compressed using single punch tablet machine. (Cadmach,Machines Ltd Ahmedabad, India) Formulation with Sodium Alginate as hydrogel plug (FP5 to FP8) Sodium alginate, spray dried lactose were mixed for 10 minutes. Magnesium stearate (1%) was added to the previous mixture and further blended for 5 minutes and compressed using single punch tablet machine. (Cadmach, Machines Ltd Ahmedabad, India) Formulation with Guargum as hydrogel plug (FP9 to FP12) Guargum, spray dried lactose were mixed for 10 minutes. Magnesium stearate (1%) was added to the previous mixture and further blended for 5 minutes and compressed using single punch tablet machine. (Cadmach, Machines Ltd Ahmedabad, India).

2 8.2 Evaluation of Hydrogel Plug (Mahajan et al.,2010) Physicochemical Characterization of Hydrogel plug Different erodible Hydrogel plugs were prepared by direct compression method. The results of Micromeritic properties are presented in Table 8.2.Hydrogel plugs were studied for hardness and weight variation Determine Hardness of Hydrogel Plug The hardness of Hydrogel Plug was measured by using Pfizer hardness tester. six Hydrogel Plugs were used for hardness uniformity studies. The data was used to calculate mean and standard deviation Determination of the time of erosion of the plugs (Lag Time) The time for complete erosion of the plugs (compressed plugs) was determined with a disintegration testing apparatus (Cintex Industrial Corporation, Dadar, Mumbai), 900 ml ph 6.8 phosphate buffer USP XXIII, 37±0.5 0 C Determination of Swelling Index of Hydrogel Plug Hydrogel plugs were taken in two different weights like 90mg, 100mg and kept immersed in three different ph conditions. (A.Meena, B.Kumar et al., 2011)Plugs were taken out carefully at 2, 4,6,8,10,12 hors intervals and weighted accurately was determined. Wet weight dry weight % swelling = X 100 Wet weight

3 Table 8.1: Composition of Hydrogel Plug S.No CONTENT OF FORMULATIONS (mg) FORMULATIONS OF HYDROGEL PLUG FP1 FP2 FP3 FP4 FP5 FP6 FP7 FP8 FP9 FP10 FP11 FP12 1. Hydroxy propyl methyl cellulose(hpmc) 2. Guargum Sodium alginate Spray dried lactose Magnesium stearate Total weight

4 8.2 Evaluation of Hydrogel Plug RESULTS & DISCUSSION Table 8.2: Physicochemical Characterization of Hydrogel plug S. NO. FORMULATIONS WEIGHT OF HYDROGE L PLUG(mg) HARNESS Kg/CM 2 *±SD LAGTIME (MINUTES)*± SD LAGTIME (HOURS) 1 FP ± ±0. 5hours 25min 2 FP ± ±0. 6hours 13min 3 FP ± ±0. 6hours 50mins 4 FP ± ±0. 7hours 25mins 5 FP ± ± hours 46mins 6 FP ± ± FP ± ± FP ± ± FP ± ± hours 40mins 5hours 48mins 6hours 30mins 3hours 11mins 10 FP ± ± hours 55mins 11 FP ± ± hours 12 FP ± ± hours 53mins *All values are represented as mean + standard deviation (n=6) 148

5 WEIGHT,HARDNESS,LAGTIME OF HYDROGEL PLUG PHYSICOCHEMICAL CHARACTERIZATION OF HYDROGEL PLUG WEIGHT OF HYDROGEL PLUG(Mg) HARNESS Kg/CM2 200 LAGTIME (MINUTES) FP1 FP2 FP3 FP4 FP5 FP6 FP7 FP8 FP9 FP10 FP11 FP12 FORMULATIONS Figure 8.1 Physicochemical Characterization of Hydrogel plug

6 8.2.4 DETERMINATION OF SWELLING INDEX OF HYDROGEL PLUG Table 8.3: Swelling Index of Different Hydrogel Plug SWELLING INDEX*±SD S. Plug NO. Materials ph 1.2 ph 7.4 ph 6.8 ph 1.2 ph 7.4 ph 6.8 ph 1.2 ph 7.4 ph 6.8 ph 1.2 ph 7.4 ph HPMC 123±0. 125±0. 128± ± ±0. 145±0. 165±0. 159±0. 164±0. 180±0. 180±0. 180±0. 2 Guargum 98± ± ± ± ±0. 118±0. 137±0. 140±0. 138±0. 155±0. 160±0. 151±0. 3 Sodium Alginate 89± ± ± ± ±0. 108± ±0. 131±0. 129±0. 145±0. 142±0. 148±0. *All values are represented as mean ± standard deviation (n=6) The weight of plug was optimized by various ph conditions like phosphate buffer ph 1.2, 6.8, 7.4 and the HPMC containing 200 mg of plug was not more change in different ph condition. So that HPMC containing 200 mg of hydrogel plug was optimized for Hydrogel plug in Pulsincap formulation. 150

7 SWELLING INDEX OF HYDROGEL PLUG SWELLING INDEX HPMC 80 GUARGUM SODIUM ALGINATE PH 1.2 0PH PH PH PH PH PH PH PH PH PH PH 6.8 HYDROGEL PLUG MATERIAL Figure 8.2 swelling index of Hydrogel plug 151

8 8.2.5 Effect of different Types of Hydrogel plug material on lag time In order to identify proper plug material, the lag times of delayed release capsule with different erodible Hydrogel plug materials were investigated. The Partial water soluble polymer like HPMC appeared attractive as Hydrogel plug materials because of their frequent use in Pulsincap. Three different Type of Polymers like HPMC, Guargum, and Sodium Alginate were evaluated. The results are shown in Figure 8.3.When comparing three different Polymers within this study it was found that capsules prepared using HPMC resulted in longer lag times. Depending on the weight of polymer matrix degrades at different rates by erosion/dissolution of the polymer this could be very advantageous, because a deviation of the amount of HPMC in the plug would result in only relatively small changes in lag time and consequently reproducible drug release profiles, with rapid and complete drug release. Therefore HPMC was selected for further study as a plug material for the preparation of the erodible tablet plug. LAG TIME(MINUTES) DIFERENT TYPES OF HYDROGEL PLUG(Mg) MATERIAL ON LAG TIME 500 HPMC FP FP1 FP6 0 FP9 FP12 HPMC GUARGUM SOD.ALGINATE HYDROGEL PLUG MATERIALS HPMC FP2 HPMC FP3 HPMC FP4 GUARGUM FP5 GUARGUM FP6 GUARGUM FP7 GUARGUM FP8 SOD.ALGINATE FP9 SOD.ALGINATE FP10 SOD.ALGINATE FP11 SOD.ALGINATE FP12 Figure 8.3 Effect of different Hydrogel plug material on lag time of timed delayed capsule device

9 8.2.6 Effect of Hydrogel Plug weight on lag time Table 8.4: EFFECT OF WEIGHT OF HYDROGEL PLUG MATERIAL ON LAG TIME S. NO. 1 2 Hydrogel Plug Materials Weight of Hydrogel Plug(Mg) Lag time (Minutes)* ±SD HPMC GUARGUM SODIUM ALGINATE FP1 FP2 FP3 FP4 FP5 FP6 FP7 FP8 FP9 FP10 FP11 FP ± 368± 390± 435± 226± 283± 347± ± 187± 213± 243± 272± *All values are represented as mean ± standard deviation (n=6) Maintaining the same composition of Hydrogel (FP1, FP2, FP3, and FP4) plugs of different weights such as 140, 160,180 and 200mg were evaluated for lag time. The relationship between plug weight and lag time is shown in Figure 8.4. A good correlation was observed between them (r 2 =0.950). Increasing tablet plug weight seemed to prolong lag time since the time required to complete the dissolution or erosion of the Hydrogel plug would be longer. This suggested that the lag time could also be adjusted by changing the plug weight. 153

10 EFFECT OF HYDROGEL PLUG WEIGHT ON LAG TIME WEIGHT & LAG TIME OF HYDROGEL PUGS Weight of Hydrogel Plug(Mg) Lag time (Minutes) FP1 FP2 FP3 FP4 FP5 FP6 FP7 FP8 FP9 FP10 FP11 FP12 HPMC GUARGUM SODIUM ALGINATE HYDROGEL PLUGS Figure 8.4 Influence of the Hydrogel Plug Weight on the Lag Time 154

11 8.2.7 Effect of HPMC content in the erodible tablet plug on drug release of timed delayed capsule device: With formulations FP1 (10mg), FP2 (20mg), FP3 (30mg) and FP4(40mg)at the end of 24th hour there was 98.26±0.860%, ±0.865%, 98.00±0.860% and ±0.857%drug was released respectively. (as shown in Table 9.4) 100 In-vitro release rate profile of FC1,FC2,FC3,FC4 containing 10mg,20mg,30mg,40mg of HPMC as Hydrogel plug % Drug Release FC1 FC2 FC3 40 FC Time(Hrs) Figure 8.5 In-Vitro Drug Release in HPMC as hydrogel plug

12 8.2.8 Effect of guar gum content in the erodible tablet plug on drug release of timed delayed capsule device: With formulations FP5 (10 mg), FP6 (20 mg),fp7(30mg) and FP8 (40 mg), at the end of 24 th hour there was 99.53±0.898%, ±0.845%, 98.96±0.860% and 97.79±0.857%,drug released respectively.(as shown in Table 9.5) 100 In-vitro release rate profile of FC5, FC6, FC7, FC8 containing 10mg,20mg,30mg,40mg of Guargum as Hydrogel Plug % Drug Release FC5 FC6 FC7 FC Time(Hrs) Figure 8.6 In-Vitro Drug Release in guar gum as hydrogel plug

13 8.2.9 Effect of sodium alginate content in the erodible tablet plug on drug release of timed delayed capsule device: With formulation FP9 (10mg),FP10 (20mg), FP11(30mg) and FP12 (40mg) at the end of 24 th hour 99.75±0.846%,97.83±0.845% 99.87%±0.844and ±0.845% drug was released respectively.(as shown in Table 9.6) 100 In-vitro release rate profile of FC9, FC10, FC11, FC12 containing 10mg,20mg,30mg,40mg of Sodium alginate as Hydrogel Plug % Drug Release FC9 FC10 FC FC Time(Hrs) Figure 8.7 In-Vitro Drug Release in sodium alginate as hydrogel plug From all the above observations, it was found that the order of sustaining capacity of Hydrogel plug polymer is HPMC > Guar gum >Sodium alginate.

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