8
Reddy Vinod M et al. IRJP 2011, 2 (9), 91-98 INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(9), 2011 INTERNATIONAL RESEARCH JOURNAL OF PHARMACY ISSN 2230 – 8407 Available online www.irjponline.com Research Article DEVELOPMENT AND EVALUATION OF MUCOADHESIVE MICROCAPSULES OF NIMODIPINE Reddy Vinod M* 1 , Patil Praveen S 2 , Biradar Karnakumar V 2 , Dana Shivshankar B 3 , D.Nagendra kumar 1 1 S.V.E.T’S College of Pharmacy Humnabad, Bidar, Karnataka, India 2 R.R.K.S College of Pharmacy Naubad Bidar, Karnataka, India 3 Karnataka College of Pharmacy, Bidar, Karnataka, India Article Received on: 10/07/11 Revised on: 11/08/11 Approved for publication: 06/09/11 *Vinod M. Reddy, Email: [email protected] ABSTRACT In the present study, the development and evaluation of Mucoadhesive microcapsules of Nimodipine has been undertaken. Nimodipine is a calcium channel blocker used in the treatment of blood pressure, angina pectoris, and myocardial infraction. However, it has a short biological half life of 1-2 hrs. Therefore, Nimodipine microcapsules were prepared with a coat consisting of Sodium Alginate and Mucoadhesive Polymers like Hydroxy Propyl Methyl Cellulose (HPMC), Carbopol 934, Sodium CMC and Methyl Cellulose in 1:1 and 1:2 ratios were prepared to make sustained release medication by Orifice-Ionic gelation process (syringe Method). Nimodipine Mucoadhesive microcapsules prepared were evaluated for various parameters like particle size analysis, Nimodipine content, micro encapsulation efficiency, % yield, In-vitro wash-off test for Drug release study, First Order Kinetics and Higuchi’s Kinetic models to explain release profile and Drug-Polymer Interaction Studies were done by IR study. All the mucoadhesive microcapsules were exhibited good mucoadhesive property in the In-vitro wash off test .However, Nimodipine with sodium Alginate – Methyl Cellulose and sodium Alginate – Carbopol 934 Microcapsules were showed sustained action for over long period of time. Further In-vivo studies are needed to optimize for sustained action in human beings. Key words – Nimodipine, Mucoadhesive Microcapsules, first order Release Kinetics and in- vitro release study INTRODUCTION Mucoadhesive dosage forms enhance the bioavailability of drugs. Greater bioavailability of testosterone and its esters, vasopressin, dopamine, insulin and gentamycin was observed from mucoadhesive dosage forms when compared to conventional dosage forms 1-5 . From the literature survey we found that, In vitro and In-vivo evaluation of mucoadhesive microcapsules of Glipizide” microcapsules exhibited good mucoadhesive property in the in vitro wash-off test. Glipizide release from these mucoadhesive microcapsules was slow and extended over longer periods of time and depended on the composition of coat of the microcapsules and preparation and evaluation of the mucoadhesive microcapsules of Indomethacin., all the microcapsules exhibited good mucoadhesive property in the in vitro wash-off test. Indomethacin release from these mucoadhesive microcapsules was slow and extended over longer periods of time and depended on the composition of coat and size of the microcapsules. Drug release was diffusion controlled and followed first order kinetics. Chemicaly Nimodipine is a Isopropyl (2- methoxyethyl) 1, 4 –dihydro –2, 6 -dimethyl – 4 – (3 – nitrophenyl) –3, 5 - pyridine - di carboxylate and having Molecular formula C 21 H 26 N 2 O 7. It is an effective calcium channel blocker, used in the treatment of subarchnoid hemorrhage, migraine and angina. It is practically insoluble in water. It has short biological half life of 1- 2hrs. Therefore, sustained release is needed for Nimodipine to give a prolonged action and reduction of usage frequency. Hence, here we designed to develop and evaluate the Mucoadhesive microcapsules of Nimodipine for its better therapeutic effectiveness. MATERIALS AND METHODS Chemicals used Nimodipine as a gift sample from Micro Labs Ltd., Bangalore, Hydropropyl Methyl, Methyl Cellulose, Sodium Carboxy Methyl Cellulose Carbopol 934, Sodium Alginate, Calcium Chloride all are procured from SD Fine Chemicals, Mumbai all the chemicals were either AR/LR grade. Instruments used Dissolution Test Apparatus (USPXXIV, TDT 06P) (Serwell Electronics JSM, Bangalore), Magnetic stirrer (Made in India), pH Meter( Elico pH Meter, Hyderabad) ,UV-Visible spectrophotometer Elico (SL-159 ver., Hyderabad),Hot air oven (Electro Lab),Weighing balance (Shimazdu Electronics), IR spectrophotometer (Sipra Lab, Hyderabad),Sieves (Jayant Scientific India, Mumbai). METHODS Orifice-Ionic gelation process (syringe Method) Microcapsules were formulated by Orifice-ionic gelation process 5, 6 , is also been successfully used to prepare large sized alginate beads. In this method Microcapsules are prepared by employing sodium alginate in combination with different polymers like sodium CMC, MC, Carbopol and HPMC as coat materials. Sodium alginate and the mucoadhesive polymer are dissolved in purified water to form a homogenous polymer solution. Core material (drug) is added to the polymer solution and mixed thoroughly to form a smooth viscous dispersion. The resulting dispersion is then added drop wise into sufficient quantity of calcium chloride (10% w/v) solution through a syringe with a needle of size No. 18. The added droplets are retained in the calcium chloride solution for 15 to 20 min. to complete the curing reaction and to produce spherical rigid microcapsules. The microcapsules are collected by decantation and the product thus separated is washed repeatedly with water and dried at 45 o C for 12 hrs. Estimation of Nimodipine content of the microcapsules Nimodipine content in the microcapsules was estimated by UV spectrophotometric method based on the measurement of absorbance at 317 nm in methanol. The results were presented in Table 1. Evaluation of microcapsules Size Distribution Analysis Different sizes in a batch were separated by sieving using a range of standard sieves. The amounts retained on different sieves were weighed and results were presented in Table 2. Micro Encapsulation Efficiency It was calculated using the reported formula (chowdary and srinivasa et al 2003). microencapsulation efficiency = estimated percent drug content/ Theoretical % drug content x 100. The results are presented in Table 3. Drug release study Release of Nimodipine form microcapsules of size 16/25, and 25/36 was studied in Acetate buffer of pH 4.5 (900 ml) using USP XXIV six-station Dissolution Rate Test Apparatus with a basket stirrer at 100 rpm. A sample of microcapsules equivalent to 60 mg of

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Reddy Vinod M et al. IRJP 2011, 2 (9), 91-98

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(9), 2011

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY ISSN 2230 – 8407 Available online www.irjponline.com Research Article

DEVELOPMENT AND EVALUATION OF MUCOADHESIVE MICROCAPSULES OF NIMODIPINE

Reddy Vinod M*1, Patil Praveen S2, Biradar Karnakumar V2, Dana Shivshankar B3, D.Nagendra kumar1 1S.V.E.T’S College of Pharmacy Humnabad, Bidar, Karnataka, India

2R.R.K.S College of Pharmacy Naubad Bidar, Karnataka, India 3Karnataka College of Pharmacy, Bidar, Karnataka, India

Article Received on: 10/07/11 Revised on: 11/08/11 Approved for publication: 06/09/11

*Vinod M. Reddy, Email: [email protected]

ABSTRACT In the present study, the development and evaluation of Mucoadhesive microcapsules of Nimodipine has been undertaken. Nimodipine is a calcium channel blocker used in the treatment of blood pressure, angina pectoris, and myocardial infraction. However, it has a short biological half life of 1-2 hrs. Therefore, Nimodipine microcapsules were prepared with a coat consisting of Sodium Alginate and Mucoadhesive Polymers like Hydroxy Propyl Methyl Cellulose (HPMC), Carbopol 934, Sodium CMC and Methyl Cellulose in 1:1 and 1:2 ratios were prepared to make sustained release medication by Orifice-Ionic gelation process (syringe Method). Nimodipine Mucoadhesive microcapsules prepared were evaluated for various parameters like particle size analysis, Nimodipine content, micro encapsulation efficiency, % yield, In-vitro wash-off test for Drug release study, First Order Kinetics and Higuchi’s Kinetic models to explain release profile and Drug-Polymer Interaction Studies were done by IR study. All the mucoadhesive microcapsules were exhibited good mucoadhesive property in the In-vitro wash off test .However, Nimodipine with sodium Alginate – Methyl Cellulose and sodium Alginate – Carbopol 934 Microcapsules were showed sustained action for over long period of time. Further In-vivo studies are needed to optimize for sustained action in human beings. Key words – Nimodipine, Mucoadhesive Microcapsules, first order Release Kinetics and in- vitro release study INTRODUCTION Mucoadhesive dosage forms enhance the bioavailability of drugs. Greater bioavailability of testosterone and its esters, vasopressin, dopamine, insulin and gentamycin was observed from mucoadhesive dosage forms when compared to conventional dosage forms1-5. From the literature survey we found that, In vitro and In-vivo evaluation of mucoadhesive microcapsules of Glipizide” microcapsules exhibited good mucoadhesive property in the in vitro wash-off test. Glipizide release from these mucoadhesive microcapsules was slow and extended over longer periods of time and depended on the composition of coat of the microcapsules and preparation and evaluation of the mucoadhesive microcapsules of Indomethacin., all the microcapsules exhibited good mucoadhesive property in the in vitro wash-off test. Indomethacin release from these mucoadhesive microcapsules was slow and extended over longer periods of time and depended on the composition of coat and size of the microcapsules. Drug release was diffusion controlled and followed first order kinetics. Chemicaly Nimodipine is a Isopropyl (2-methoxyethyl) 1, 4 –dihydro –2, 6 -dimethyl – 4 – (3 – nitrophenyl) –3, 5 - pyridine - di carboxylate and having Molecular formula C21 H26 N2 O7. It is an effective calcium channel blocker, used in the treatment of subarchnoid hemorrhage, migraine and angina. It is practically insoluble in water. It has short biological half life of 1-2hrs. Therefore, sustained release is needed for Nimodipine to give a prolonged action and reduction of usage frequency. Hence, here we designed to develop and evaluate the Mucoadhesive microcapsules of Nimodipine for its better therapeutic effectiveness. MATERIALS AND METHODS Chemicals used Nimodipine as a gift sample from Micro Labs Ltd., Bangalore, Hydropropyl Methyl, Methyl Cellulose, Sodium Carboxy Methyl Cellulose Carbopol 934, Sodium Alginate, Calcium Chloride all are procured from SD Fine Chemicals, Mumbai all the chemicals were either AR/LR grade. Instruments used Dissolution Test Apparatus (USPXXIV, TDT 06P) (Serwell Electronics JSM, Bangalore), Magnetic stirrer (Made in India), pH Meter( Elico pH Meter, Hyderabad) ,UV-Visible spectrophotometer Elico (SL-159 ver., Hyderabad),Hot air oven (Electro Lab),Weighing balance (Shimazdu Electronics), IR

spectrophotometer (Sipra Lab, Hyderabad),Sieves (Jayant Scientific India, Mumbai). METHODS Orifice-Ionic gelation process (syringe Method) Microcapsules were formulated by Orifice-ionic gelation process5, 6, is also been successfully used to prepare large sized alginate beads. In this method Microcapsules are prepared by employing sodium alginate in combination with different polymers like sodium CMC, MC, Carbopol and HPMC as coat materials. Sodium alginate and the mucoadhesive polymer are dissolved in purified water to form a homogenous polymer solution. Core material (drug) is added to the polymer solution and mixed thoroughly to form a smooth viscous dispersion. The resulting dispersion is then added drop wise into sufficient quantity of calcium chloride (10% w/v) solution through a syringe with a needle of size No. 18. The added droplets are retained in the calcium chloride solution for 15 to 20 min. to complete the curing reaction and to produce spherical rigid microcapsules. The microcapsules are collected by decantation and the product thus separated is washed repeatedly with water and dried at 45 oC for 12 hrs. Estimation of Nimodipine content of the microcapsules Nimodipine content in the microcapsules was estimated by UV spectrophotometric method based on the measurement of absorbance at 317 nm in methanol. The results were presented in Table 1. Evaluation of microcapsules Size Distribution Analysis Different sizes in a batch were separated by sieving using a range of standard sieves. The amounts retained on different sieves were weighed and results were presented in Table 2. Micro Encapsulation Efficiency It was calculated using the reported formula (chowdary and srinivasa et al 2003). microencapsulation efficiency = estimated percent drug content/ Theoretical % drug content x 100. The results are presented in Table 3. Drug release study Release of Nimodipine form microcapsules of size 16/25, and 25/36 was studied in Acetate buffer of pH 4.5 (900 ml) using USP XXIV six-station Dissolution Rate Test Apparatus with a basket stirrer at 100 rpm. A sample of microcapsules equivalent to 60 mg of

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Reddy Vinod M et al. IRJP 2011, 2 (9), 91-98

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(9), 2011

Nimodipine was used in each test. Samples were withdrawn through a filter at different intervals and were assayed at 317 nm for Nimodipine using a Shimadzu UV-150 double-beam spectrophotometer. The drug release experiments were conducted in triplicate. The results were presented in Table 4 to 11. In-vitro wash-off test for Mucoadhesive Microcapsules The mucoadhesive property of the microcapsules was evaluated by an in vitro adhesion testing method known as wash-off method. A piece of intestinal mucous (2x2 cm) was mounted on to glass slides of (3x1 inch) with Cyanoacrylate glue. Two glass slides were connected with a suitable support. About 50 microcapsules were spread on to each wet tissue specimen and there after the support was hung on to the arm of a USP tablet disintegrating test machine. The disintegration machine containing tissue specimen was adjusted at slow, regular up and down moment in a test fluid at 37 oC taken in a beaker. AT the end of 30 min., 1 hr and later at hourly intervals up to 6 hrs, the machine was stopped and the number of microcapsules still adhering on to the tissue was counted. The test was performed in acetate buffer of pH 4.5. The results were presented in Table 12. Drug-Polymer Interaction Studies The IR spectra of the pure drug and Mucoadhesive Microcapsules were shown in figure 2. The characteristic peak (N-H=3298.28 cm-1) Mucoadhesive Microcapsules in the spectra were found to be super imposable to that of pure drug and there are no extra peaks, which gives an evidence that the drug is intact in Mucoadhesive polymers. RESULT AND DISCUSSION The formulae of Mucoadhesive Microcapsules were given in Table – 13. Microcapsules of Nimodipine with a coat consisting of Sodium Alginate and Mucoadhesive polymers namely sodium CMC, methylcellulose, HPMC and Carbopol in 1:1 and 1:2 ratios were prepared by the Orifice-ionic gelation process. Standard graph of Nimodipine in Methanol were shown in Fig – 1 and results are presented in Table- 14. Good linearity was observed with the plot. It’s ‘r’ value is 0.9953 and hence, obeyed Beer-Lambert’s law in the concentration range of 5 – 30 mg/ml. The percentage of drug content in Microcapsules was found to be 21.86(SCMC) – 38.49 %( Carbopol) and drug entrapment was found to be 51.18(HPMC) – 76.44 %( Carbopol 934). The entrapment efficiency of drug was gradually decreased in the order of Carbopol<MC<SCMC<HPMC. The results of the drug content uniformity in each of Microcapsules were presented in Table – 1. The IR spectra of the pure drug and Mucoadhesive Microcapsules were shown figure 2. The characteristic peak (N-H=3298.28 cm-1) Mucoadhesive Microcapsules in the spectra was found to be super imposable to that of pure drug and there are no extra peaks, which gives an evidence

that the drug is intact in Mucoadhesive polymers. The dissolution rate studies were performed by using USP-XXIV dissolution apparatus employing rotating paddle at a speed of 100 rpm in the dissolution medium of Acetate buffer of pH 4.5 and study was continued up to 10 hrs at suitable time intervals, samples of 5ml were withdrawn by means of pipette and it was immediately replaced with fresh dissolution medium. The withdrawn samples were analyzed for the drug content after appropriate dilutions by measuring the absorbance at 317 nm with UV spectrophotometer. The dissolution data were analyzed by computer and it was observed that the release profile of Microcapsules followed First Order release kinetics and Higuchi’s Square root plot. Nimodipine release from these Microcapsules was sustained over a prolonged period of time. The drug release data and the drug release profiles were shown in Tables – 4 – 11. The prepared Microcapsules were found to be discrete, large, spherical and free flowing and having uniform size. The size analysis is shown in Table – 10. It was showed that about 48.47% and 63.53% were in the size range of 25/36. Micro encapsulation efficiency was calculated and the results were present in Table – 11. The results of Micro encapsulation efficiency were found in the range of 65.64 – 79.78% with Sodium CMC having 65.64% and HPMC having 79.78%. The results of Mucoadhesive Microcapsules were presented in Table – 12 and showed fairly good Mucoadhesive property of Microcapsules in all the cases. CONCLUSION The order of increasing release rate observed with various mucoadhesive microcapsules of Nimodipine with sodium alginate – methyl cellulose < Sodium Alginate – Carbopol < Sodium Alginate – Sodium CMC < Sodium Alginate – HPMC. In conclusion, Sodium Alginate – Methyl Cellulose and Sodium Alginate – Carbopol 934 microcapsules could be used for sustained action for over long period of time. However, further In-vivo studies are needed to optimize for sustained action in human beings for their better efficacy and safety. REFERENCES 1. Voorspoel J and Remon J et al. Mucoadhesive microspores a promising fool in

drug delivary system. Int. Symp, Control Re. Bioact. Mater 1994; 21: 539-43. 2. Morimoto K, Yamaguchi H et al, improved ocular penetration of getamicin by

mucoadesives. Pharm. Res 1991; 8: 471-474. 3. Ikeda K, Murata K et al. formulation and evaluation of propranolol hydrochloride

leaded microcapsules.Chem. Pharm. Bull 1992; 40: 2155-58. 4. Nagai T et al, Design and in vitro and in –vivo evaluation of mucoadhesive

microcapsule. J. Controlled Release. 1984; 1:15-22. 5. Kim CK and Lee EJ. Design and in vitro and in vivo evaluation of mucoadhesive

microcapsules of indomethacin. Int. J. Pharm 1992; 79: 11-19. 6. Hari PC, Chandy T and Sharma CP, formulation and characterization of rifampicin

microcapsules. J. Microencapsul 1996; 13:319-23 .

Table -1.Assay of Prepared Micro Capsules

Sl. No Formulations D/P ratio % drug content % drug entrapment

1 MH1 1:1 34.79 51.18

2 MH2 1:2 26.57 56.92 3 MS1 1:1 33.02 64.89 4 MS2 1:2 21.86 62.82

5 MC1 1:1 38.49 76.44

6 MC2 1:2 24.93 66.18

7 MM1 1:1 37.43 72.25

8 MM2 1:2 25.01 67.82

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Reddy Vinod M et al. IRJP 2011, 2 (9), 91-98

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(9), 2011

Table-2.Sieve Analysis of Micro Capsules

Sl. No

Sieve No

Size range

(mmmmm)

Formulation (% weight retained)

MH1 MH2 MS1 MS2 MC1 MC2 MM1 MM2

1 Below 36

425

6.96

7.74

4.31 7.92

6.54

5.84 5.74

7.55

2 25/36

425-600

61.46

53.42

57.96

48.47

63.53

59.72

55.53

53.24

3

16/25

600-1000 22.46

28.34

27.24 33.23

18.82

23.54

20.03 22.15

4

Above 16 1000 9.11s 10.40 10.49 10.38 11.10 10.80 18.70 13.16

Table-3. Micro Encapsulation Efficiency of Micro Capsules

Sl. No

Formulations

Weight taken

(mg)

Theoretical drug

content (mg)

Practical drug

content (mg±±±±SD)*

Encapsulation efficiency (%)

Weight of micro capsules

equivalent to 15 mg of drug (mg)

1 MH1

100

50 34.79 69.58

21.5

2

MH2

100

33.3 26.57 79.78

18.79

3

MS1

100

50 33.02 66.04

22.71

4 MS2 100 33.3 21.86 65.64 22.84

5 MC1

100 50 38.49 76.98 19.48

6 MC2 100 33.3 24.93 74.86 20.03

7

MM1

100

50 37.43 74.86

20.03

8 MM2 100 33.3 25.01 75.10 19.97

Table-4. In-vitro Drug Release Profile of Nimodipine from MH1 Formulation (#25/36)

Time (hrs.) T Log T Conc. (mcg./ml.) CDR (mg.) CDR

(%) Log % CDR

Cumulative % Drug remained

Cumulative Log % Drug remained

0.30 0.547 -0.522 15.35 13.81 23.03 1.362 76.97 1.886 1.0 1 0 19.87 17.88 29.81 1.474 70.19 1.846 2.0 1.414 0.301 23.79 21.41 35.69 1.553 64.31 1.808 3.0 1.732 0.477 27.62 24.86 41.44 1.617 58.56 1.768 4.0 2 0.602 31.62 28.45 47.41 1.676 52.59 1.721 5.0 2.236 0.698 35.52 31.97 53.29 1.727 46.71 1.669 6.0 2.449 0.778 39.47 35.52 57.20 1.757 42.8 1.631 7.0 2.645 0.845 43.39 39.05 65.09 1.814 34.91 1.543 8.0 2.828 0.903 47.00 42.30 70.50 1.848 29.50 1.470

9.0 3 0.954 51.24 46.11 76.85 1.886 23.15 1.365

10.0 3.162 1 54.48 49.03 81.73 1.912 18.27 1.262 *Each reading is an average of three determinations

Table-5. In-vitro Drug Release Profile of Nimodipine from MH2 Formulation (#25/36)

Time (hrs.) T Log T Conc. (mcg./ml.)

CDR (mg.) CDR (%) Log %

CDR Cumulative % Drug remained

Cumulative Log % Drug remained

0.30 0.547 -0.522 12.69 11.42 19.04 1.280 80.97 1.908 1.0 1 0 15.47 13.92 23.21 1.366 76.80 1.885 2.0 1.414 0.301 20.29 18.26 30.44 1.483 69.57 1.842 3.0 1.732 0.477 25.09 22.58 37.64 1.576 62.37 1.795 4.0 2 0.602 28.54 25.69 42.81 1.632 57.19 1.757 5.0 2.236 0.698 32.94 29.65 49.41 1.694 50.59 1.704 6.0 2.449 0.778 36.86 33.17 55.29 1.743 44.71 1.650 7.0 2.645 0.845 40.94 36.85 61.41 1.788 38.59 1.586 8.0 2.828 0.903 43.76 39.38 65.64 1.817 34.36 1.536

9.0 3 0.954 48.56 43.70 72.84 1.862 27.16 1.434

10.0 3.162 1 51.89 46.70 77.84 1.891 22.17 1.346 *Each reading is an average of three determinations

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Reddy Vinod M et al. IRJP 2011, 2 (9), 91-98

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(9), 2011

Table-6. In-vitro drug release profile of Nimodipine from MS1 formulation (#25/36)

Time (hrs.) T Log T Conc. (mcg./ml.) CDR (mg.) CDR

(%) Log % CDR

Cumulative % Drug remained

Cumulative Log % Drug remained

0.30 0.547 -0.522 15.64 14.08 23.46 1.370 76.54 1.884 1.0 1 0 19.70 17.73 29.55 1.471 70.45 1.848 2.0 1.414 0.301 22.74 20.47 34.11 1.533 65.89 1.819 3.0 1.732 0.477 30.01 27.01 45.02 1.653 54.99 1.740 4.0 2 0.602 31.88 28.69 47.82 1.680 52.18 1.718 5.0 2.236 0.698 35.98 32.38 53.97 1.732 46.03 1.663 6.0 2.449 0.778 41.22 37.10 61.83 1.791 38.17 1.582 7.0 2.645 0.845 44.06 39.65 66.09 1.820 33.91 1.530 8.0 2.828 0.903 48.12 43.31 72.18 1.858 27.82 1.444

9.0 3 0.954 49.41 44.47 74.12 1.870 25.89 1.413

10.0 3.162 1 52.74 47.47 79.11 1.898 20.89 1.320 *Each reading is an average of three determinations

Table-7. In-vitro drug release profile of Nimodipine from MS2 formulation (#25/36)

Time (hrs.) T Log T Conc. (mcg./ml.) CDR (mg.) CDR (%) Log %

CDR Cumulative % Drug remained

Cumulative Log % Drug remained

0.30 0.547 -0.522 16.72 15.05 25.08 1.399 74.92 1.875 1.0 1 0 21.36 19.22 32.04 1.506 67.96 1.832 2.0 1.414 0.301 25.47 22.92 38.21 1.582 61.80 1.791 3.0 1.732 0.477 30.67 27.60 46.01 1.663 54.00 1.732 4.0 2 0.602 35.44 31.90 53.16 1.726 46.84 1.671 5.0 2.236 0.698 38.67 34.80 58.01 1.763 42.00 1.623 6.0 2.449 0.778 40.71 36.64 61.07 1.786 38.94 1.590 7.0 2.645 0.845 43.45 39.11 65.18 1.814 34.83 1.542 8.0 2.828 0.903 45.42 40.88 68.13 1.833 31.87 1.503

9.0 3 0.954 47.46 42.71 71.19 1.852 28.81 1.460

10.0 3.162 1 50.70 45.63 76.05 1.881 23.95 1.379 *Each reading is an average of three determinations

Table-8. In-vitro drug release profile of Nimodipine from MC1 formulation (#25/36)

Time (hrs.) T Log T Conc. (mcg./ml.)

CDR (mg.)

CDR (%)

Log % CDR

Cumulative % Drug remained

Cumulative Log % Drug remained

0.30 0.547 -0.522 18.26 16.43 27.39 1.438 72.61 1.861 1.0 1 0 22.98 20.68 34.47 1.537 65.53 1.816 2.0 1.414 0.301 27.71 24.94 41.57 1.619 58.44 1.767 3.0 1.732 0.477 32.44 29.20 48.66 1.687 51.34 1.710 4.0 2 0.602 37.16 33.44 55.74 1.746 44.26 1.646 5.0 2.236 0.698 40.53 36.48 60.80 1.784 39.21 1.593 6.0 2.449 0.778 42.76 38.48 64.14 1.807 35.86 1.555 7.0 2.645 0.845 45.46 40.91 68.19 1.834 31.81 1.503 8.0 2.828 0.903 48.12 43.31 72.18 1.858 27.82 1.444

9.0 3 0.954 49.45 44.51 74.18 1.870 25.83 1.412

10.0 3.162 1 52.50 47.25 78.75 1.896 21.25 1.327 *Each reading is an average of three determinations

Table-9. In-vitro drug release profile of Nimodipine from MC2 formulation (#25/36)

Time (hrs.) T Log T Conc. (mcg./ml.) CDR (mg.) CDR

(%) Log % CDR

Cumulative % Drug remained

Cumulative Log % Drug remained

0.30 0.547 -0.522 13.72 12.35 20.58 1.313 79.42 1.900 1.0 1 0 17.14 15.43 25.71 1.410 74.29 1.871 2.0 1.414 0.301 21.86 19.67 32.79 1.516 67.21 1.827 3.0 1.732 0.477 25.95 23.36 38.93 1.590 61.08 1.786 4.0 2 0.602 30.14 27.13 45.21 1.655 54.79 1.739 5.0 2.236 0.698 35.16 31.64 52.74 1.722 47.26 1.674 6.0 2.449 0.778 37.20 33.48 55.80 1.747 44.20 1.645 7.0 2.645 0.845 42.33 38.10 63.50 1.803 36.51 1.562 8.0 2.828 0.903 45.78 41.20 68.67 1.837 31.33 1.496

9.0 3 0.954 47.35 42.62 71.03 1.851 28.98 1.462

10.0 3.162 1 50.40 45.36 75.60 1.879 24.40 1.387 *Each reading is an average of three determinations

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Reddy Vinod M et al. IRJP 2011, 2 (9), 91-98

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(9), 2011

Table-10. In-vitro drug release profile of Nimodipine from MM1 formulation (#25/36)

Time (hrs.) T Log T Conc. (mcg./ml.) CDR (mg.) CDR

(%) Log % CDR

Cumulative % Drug remained

Cumulative Log % Drug remained

0.30 0.547 -0.522 12.66 11.39 18.99 1.279 81.01 1.909 1.0 1 0 15.02 13.52 22.53 1.353 77.47 1.889 2.0 1.414 0.301 17.41 15.67 26.12 1.417 73.89 1.869 3.0 1.732 0.477 21.92 19.73 32.88 1.517 67.12 1.827 4.0 2 0.602 26.34 23.71 39.51 1.597 60.49 1.782 5.0 2.236 0.698 30.83 27.75 46.25 1.665 53.76 1.730 6.0 2.449 0.778 35.28 31.75 52.92 1.724 47.08 1.673 7.0 2.645 0.845 37.08 33.37 55.62 1.745 44.38 1.647 8.0 2.828 0.903 38.80 34.92 58.20 1.765 41.80 1.621

9.0 3 0.954 42.71 38.44 64.07 1.807 35.94 1.556

10.0 3.162 1 46.11 41.50 69.17 1.840 30.84 1.489 *Each reading is an average of three determinations

Table-11. In-vitro drug release profile of Nimodipine from MM2 formulation (#25/36)

Time (hrs.) T Log T Conc.

(mcg./ml.) CDR (mg.)

CDR (%)

Log % CDR

Cumulative % Drug remained

Cumulative Log % Drug remained

0.30 0.547 -0.522 11.48 10.33 17.22 1.236 82.78 1.918 1.0 1 0 13.49 12.14 20.24 1.306 79.77 1.902 2.0 1.414 0.301 15.64 14.08 23.46 1.370 76.54 1.884 3.0 1.732 0.477 20.05 18.05 30.08 1.478 69.93 1.845 4.0 2 0.602 24.47 22.02 36.71 1.565 63.30 1.801 5.0 2.236 0.698 27.38 24.64 41.07 1.614 58.93 1.770 6.0 2.449 0.778 31.18 28.06 46.77 1.670 53.23 1.726 7.0 2.645 0.845 33.74 30.37 50.61 1.704 49.39 1.694 8.0 2.828 0.903 37.14 33.43 55.71 1.746 44.29 1.646

9.0 3 0.954 40.67 36.60 61.01 1.785 39.00 1.591

10.0 3.162 1 43.40 39.06 65.10 1.814 34.90 1.543 11.0 0.316 1.41 46.74 42.07 70.11 1.846 29.89 1.476 12.0 3.464 1.079 50.08 45.07 75.12 1.876 24.88 1.396

*Each reading is an average of three determinations

Table-12. Results of In-vitro Wash – Off Test to Assess Mucoadhesive Property of the Microcapsules

S. No.

Microcapsules Percent Microcapsules adhering to tissue at (h)

Acetate buffer, pH 4.5

1 2 4 6 8

1 MH1 66 (1.5)

51 (2)

20 (2)

06 (2)

-

2 MH2 71 (0.5)

56 (1.5)

27 (0.5)

10 (1)

04 (1.5)

3 MS1 27 (2)

15 (1)

10 (2)

01 (1)

-

4 MS2 32 (0.5)

19 (1)

14 (0.5)

05 (0.5)

-

5 MC1 63 (0.5)

60 (0.5)

25 (1)

14 (1)

-

6 MC2 69 (1.5)

65 (2)

32 (2)

19 (2)

15 (0.5)

7 MM1 57 (0.5)

37 (1.5)

12 (0.5)

- -

8 MM2 61 (0.5)

43 (1)

14 (0)

- -

Figures in Parenthesis are Standard Deviation Value

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Reddy Vinod M et al. IRJP 2011, 2 (9), 91-98

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(9), 2011

Table-13. Formulae of Mucoadhesive Microcapsules S.No Ingredients Quantity used in Formulations (gms)

MH1

MH2

MS1 MS2

MC1

MC2

MM1 MM2

1 Nimodipine 2 1 2 1 2 1 2 1

2 HPMC 1 1 - - - - - -

3 SCMC - - 1 1 - - - -

4 Carbopol - - - - 1 1 - -

5 MC - - - - - - 1 1

6 Sod. Alginate 1 1 1 1 1 1 1 1

7 Total Weight 4 3 4 3 4 3 4 3

8 Drug: Polymer 1:1 1:2 1:1 1:2 1:1 1:2 1:1 1:2

Table-14. Absorbance of Standard Curve for Nimodipine in Methanol

Sl.No. Concentration (mmmmg/ml) Absorbance* 1 5 0.071

2 10 0.159

3 15 0.198

4 20 0.268

5 25 0.328

6 30 0.397

*Average of 3 determination

Figure-1. Calibration Curve For the Estimation of Nimodipine in methanol 317nm)

Standard Calibration curve of Nimodipine in Methanol

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0.45

0 5 10 15 20 25 30 35

Conc (mcg/ml)

Absorbance

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Reddy Vinod M et al. IRJP 2011, 2 (9), 91-98

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(9), 2011

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Reddy Vinod M et al. IRJP 2011, 2 (9), 91-98

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY, 2(9), 2011

Figure-2. Drug and polymers interactions were showed using IR reports as follows a) pure drug Nimodipine,b) Nimodipine with sodium cmc c) Nimodipine with methyl cellulose d) Nimodipine with HPMC e) Nimodipine with carbopol 934 respectively.

Source of support: Nil, Conflict of interest: None Declared