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Abstract

The objectives of the present investigation was to formulate and evaluate Ramipril Microspheres by using different polymers such as HPMC K-4M, HPMCK-15M, HPMCK-100M and Ethyl Cellulose. The shape of microspheres were characterized by optical microspheres and surface morphology evaluated by scanning electron microscopy. Other evolutionary parameters such as Entrapment efficiency, Buoyancy study, In-vitro study was studied. The buoyancy study compliances the floating behavior of microspheres. In-vitro study shows prolonged sustained release pattern of drug release. Scanning electron microscopy showed that microspheres surface was sponge like structure with porous in nature. The prepared Floating microspheres of Ramipril might be used for prolonged drug relese in GIT, for better drug action and improved patient compliance.

Keywords

Ramipril, Microspheres, Scanning electron microscopy, Entrapment efficiency, Buoyancy study, In-vitro drug release, Sustained drug release

Introduction

Floating microsphere are gastro- retentive drug delivery system. As the system floats over gastric contents, the drug is released slowly at desired rate resulting in increased gastric retention time. Floating system are low density that have sufficiently bouncy to float over gastric fluid. After release of drug, the residual system is emptied from the stomach. Attempts are being made to develop a drug delivery system which can be provide therapeutically effective plasma drug concentration for longer period thereby reducing the frequency and minimizing fluctuation in plasma drug concentration at steady state by delivering the drug in a sustained manner.

MATERIAL AND METHOD MATARIAL

Ramipril is used as active pharmaceutical ingredients, HPMC K-4M, HPMC K-15M, HPMC K-100M, Ethyl Cellulose, Sodium alginate, Calcium chloride are of standard grade.  


Table 01: Formula for Ramipril microspheres

Ingredients (mg)

F1

F2

F3

F4

F5

F6

F7

F8

F9

Ramipril

10

10

10

10

10

10

10

10

10

HPMC K -4M

30

50

70

---

---

---

---

---

---

HPMC K -15M

---

---

---

30

50

70

---

---

---

HPMC K -100M

---

---

---

---

---

---

30

50

70

Ethyl cellulose

10

10

10

10

10

10

10

10

10

Sodium alginate

3000

3000

3000

3000

3000

3000

3000

3000

3000

Calcium chloride

2000

2000

2000

2000

2000

2000

2000

2000

2000

 

U.V Scanning:


       
            Figure No. 01 UV spectrum of Ramipril.png
       

Figure No. 01: UV spectrum of Ramipril


? max of was found to be 206 nm in 1.2 acidic buffer of PH 1.2. Hence further study was carried out at 206 nm in pH 1.2 acidic buffer.

Standard calibration curves:


Table 02: Calibration curves in 0.1 N HCL

Sr.no.

Concentration (µg/ml)

Absorbance

1

00

00

2

02

0.096

3

04

0.180

4

06

0.268

5

08

0.365

6

10

0.447

7

12

0.540

8

14

0.643

9

16

0.719

10

18

0.818

11

20

0.916

12

22

1.035


       
            Figure No. 02 Calibration curve of Ramipril in 0.1 N HCl.png
       

Figure No.02: Calibration curve of Ramipril in 0.1 N HCl


DSC:


       
            Figure No. 03 DSC of pure drug Ramipril.png
       

Figure No. 03: DSC of pure drug Ramipril


       
            Figure No. 04 DSC of formulation.png
       

Figure No. 04: DSC of formulation


DSC Thermograms of pure Ramipril, blend of polymer with drug were determined. Pure Ramipril showed a sharp onset of peak at 109o C corresponding to its melting point. There was no appreciable change in the melting endotherms of physical mixture compared to that of pure drug Ramipril. Absence of any new endothermic peak or disappearance or shit of endothermic peak confirms that there is no any interaction and hence the polymers are compatible with drug.

SEM:


       
            Figure No. 05 Figures of SEM of Microspheres2.tif
       


       
            Figure No. 05 Figures of SEM of Microspheres1.tif
       

Figure No. 05: Figures of SEM of Microspheres


The microspheres were spherical and the external surface was smooth with slightly rough surface  which could be due to drying. The internal surface of microspheres showed sponge like nature.

Evaluation Of Floating Microspheres For Floating Parameters:


Table 03: %Yield, mean particle size, angle of repose of microspheres

Formulation code

% yield

Mean particle size

Angle of repose

F1

92.83 ± 0.275

820 ± 1.520

26.12 ± 0.103

F2

94.43 ± 0.376

870 ± 1.007

28.07 ± 0.001

F3

90.23 ± 1.495

865 ± 2.065

19.65 ± 0.565

F4

82.10 ± 3.181

840 ± 3.105

12.95 ± 0.589

F5

88.63 ± 0.988

811 ± 4.187

16.52 ± 0.722

F6

89.88 ± 0.957

841 ±  0.174

16.12 ± 0.405

F7

95.75 ± 2.326

830 ± 5.0132

15.79 ± 0.400

F8

80.76 ± 0.668

865 ± 0.421

20.19 ± 0.182

F9

95.62 ± 0.490

841 ± 2.0174

16.59 ± 0.230


Table 04: entrapment efficiency, in vitro buoyancy, % drug release of ramipril microspheres

Formulation code

Entrapment efficiency

In-vitro buoyancy

%  drug release

F1

89 ± 10.4

12+

85.74 ± 0.502

F2

85 ± 2.645

12+

80.31 ± 0.654

F3

85.66 ± 3.511

12+

82.41 ± 0.195

F4

83.66 ± 3.785

12+

86.04 ± 0.627

F5

86.66 ±1.527

12+

82.54 ± 0.401

F6

89.66 ± 21.45

12+

85.98 ± 0.598

F7

93.33 ± 0.577

12+

86.31 ± 0.185

F8

87 ± 15.099

12+

85.53 ± 0.697

F9

89.33 ± 9.865

12+

84.23 ± 2.081


Table 05: % Drug release study of ramipril microspheres (f1 –f5)

Time

( Hr )

% Release

F1

F2

F3

F4

F5

1

15.93 ± 0.109

22.57 ± 0.775

21.64 ± 0.775

21.64 ± 0.775

19.50 ± 1.216

2

27.36 ± 0.405

25.22 ± 0.995

25.22 ± 0.995

28.65 ± 1.028

31.70 ± 3.273

3

32.74 ± 0.334

36.45 ± 0.687

36.71 ± 0.687

36.71 ± 0.687

37.75 ± 0.401

4

37.94 ± 0.591

42.68 ± 0.385

42.88 ± 0.512

46.71 ± 0.687

42.22 ± 0.420

5

53.78 ±  0.975

52.69 ± 0.465

53 ± 0.675

54.62 ± 0.876

57.84 ± 0.450

6

60.62 ± 0.332

60.08 ± 0.681

59.88 ± 0.295

59.95 ± 0.225

59.89 ± 0.410

7

64.88 ± 0.327

64.06 ± 3.352

65.99 ± 0.687

63.65 ± 0.488

62.93 ± 1.276

8

70.27 ± 0.625

73.65 ± 0.390

75.07 ± 0.976

69.75 ± 0.700

73.87 ± 1.153

9

77.91 ± 0.226

77.57 ± 0.497

77.62 ± 0.845

77.47± 0.562

79.16 ± 0.405

10

79.29 ± 0.190

78.58 ± 0.594

80.72 ± 1.403

82.28 ± 1.460

81.31 ± 0.295

11

85.74 ± 0.502

80.31 ± 0.654

82.41 ± 0.195

86.04 ± 0.627

82.54 ± 0.401


Table 06: % drug release study of ramipril microspheres (f6 – f9)

Time

( Hr )

% Release

F6

F7

F8

F9

1

19.83 ± 1.476

19.37 ± 1.072

21.91 ± 0.436

14.24 ± 0.780

2

24.57 ± 0.334

28.87 ± 1.203

28.65 ± 1.028

28.01 ± 0.900

3

37.48 ± 0.788

37.23 ± 0.519

37.23 ± 0.519

34.63 ± 2.439

4

41.87 ± 1.842

43 ± 0.300

43 ± 0.300

37.81 ± 0.190

5

51.37 ± 1.106

51.37 ± 1.106

54.62 ± 0.876

58.65 ± 1.350

6

61.71 ± 1.240

60.02 ± 0.195

59.89 ± 0.127

60.65 ± 1.350

7

64.04 ± 1.105

63.65 ± 0.488

64.35 ± 0.872

64.43 ± 1.144

8

68.71 ± 0.709

69.03 ± 1.170

71.81 ± 3.366

68.90 ± 1.001

9

78.64 ± 0.790

77.49 ± 2.619

76.50 ± 0.957

79.81 ± 0.740

10

81.31 ± 0.225

82.34 ± 1.409

81.37 ± 0.295

83.77 ± 2.361

11

85.98 ± 0.598

86.31 ± 0.185

85.53 ± 0.697

84.23 ± 2.081


       
            Figure No. 06 % Release of drug of formulations (F-F3).png
       

Figure No.06: % Release of drug of formulations (F-F3)


       
            Figure No. 07 % Release of drug of formulations (F4-F6).png
       

Figure No.07: % Release of drug of formulations (F4-F6)


       
            Figure No. 08 % Release of drug of formulations (F7-F9).png
       

Figure No. 08: % Release of drug of formulations (F7-F9)


 

 

Stability Study:

Stability study of optimized best batch F7 at temperature 40 ± 2oC and relative humidity 75 ± 5%


Table 07: Stability study of best batch

Sr. no.

Time

Appearance

% drug entrapment

Floating

% drug release

1

0

White

93.33 ± 0.577

12+

86.31 ± 0.185

2

30 days

White

92.69 ± 1.684

12+

86.5 ± 0.400

3

60 days

White

93.32 ± .0.912

12+

86.96 ± 0.550

4

90 days

White

93.41 ± 0.167

12+

86.78 ± 0.436


CONCLUSION

Microspheres of Ramipril can be successfully prepared using various polymers such as HPMC , Ethyl cellulose. The % yield of all microspheres formulation was more than 75% suggesting that method used for encapsulation was effective. Particle size of all formulation was in range of 810 to 870 µm. The entrapment efficiency was good in all batches. The in vitro buoyancy was after 12 hrs indicated satisfactory performance of proposed formulation. The flow properties of of all prepared microspheres were good as indicated.  The good flow properties suggested that the microspheres produced were no aggregated. The % release microspheres were found to be order F7< F4>

REFERENCE

  1. Pandey N, Negi A, Mahara K, Formation and evaluation of floating Microspheres of Nateglinide. International Journal of Pharma Science and Research 2016;7(11):453-464.
  2. Kapoor D, Patel R, Formulation Optimization and evaluation of floating Microspheres of Captopril. Asian Journal of Biomedical and Pharmaceutical Science 2012;2(9) 1-10.
  3. Gadad A, Naik S, Panchaxari M, Bolmal U, Formulation and evaluation of Gastrotrntive floating Microspheres of Lafutidine. Indian Journal of Pharmaceutical Education and Research 2016;50(2) 576-581.
  4. Gaythridevi M, Adlin J, Floating microspheres : A review. International Journal of Research and Chemistry 2016;6(3).504.
  5. Negi R, Microbaloons : A better approach for gastro retention. Indian Journal of Pharmaceutical and Biological Research 2014;2(2) 100-107.
  6. Bansal H, Simar Preet Kaur, Microspheres : method of prepration and application a comparative study. International Journal of Pharmaceutical Science Review and Research 2011;10(1) 69-78.
  7. Kadam N, Suvarna V, Microspheres : A brief review. Asian Journal of Biomedical and Pharmaceutical Science 2015; 5(47) 13-19..
  8. Metkari V, Kulkarni L, Patil P, Jadhav P,  Bomane G, Kumbhar C, Microspheres – A new drug delivery system : a review. Journal of Current Pharma Research2014;4(2) 1128-1133.
  9. Ratnaparkhi M, Dhiwar S, Dhage K, Bhore S, Kadam P, Patil P, Formulation and invitro characterization of floating microspheres of Metformin HCl. Der Pharmacia Lettre, 2012;4(5) 1390-1400.

Reference

  1. Pandey N, Negi A, Mahara K, Formation and evaluation of floating Microspheres of Nateglinide. International Journal of Pharma Science and Research 2016;7(11):453-464.
  2. Kapoor D, Patel R, Formulation Optimization and evaluation of floating Microspheres of Captopril. Asian Journal of Biomedical and Pharmaceutical Science 2012;2(9) 1-10.
  3. Gadad A, Naik S, Panchaxari M, Bolmal U, Formulation and evaluation of Gastrotrntive floating Microspheres of Lafutidine. Indian Journal of Pharmaceutical Education and Research 2016;50(2) 576-581.
  4. Gaythridevi M, Adlin J, Floating microspheres : A review. International Journal of Research and Chemistry 2016;6(3).504.
  5. Negi R, Microbaloons : A better approach for gastro retention. Indian Journal of Pharmaceutical and Biological Research 2014;2(2) 100-107.
  6. Bansal H, Simar Preet Kaur, Microspheres : method of prepration and application a comparative study. International Journal of Pharmaceutical Science Review and Research 2011;10(1) 69-78.
  7. Kadam N, Suvarna V, Microspheres : A brief review. Asian Journal of Biomedical and Pharmaceutical Science 2015; 5(47) 13-19..
  8. Metkari V, Kulkarni L, Patil P, Jadhav P,  Bomane G, Kumbhar C, Microspheres – A new drug delivery system : a review. Journal of Current Pharma Research2014;4(2) 1128-1133.
  9. Ratnaparkhi M, Dhiwar S, Dhage K, Bhore S, Kadam P, Patil P, Formulation and invitro characterization of floating microspheres of Metformin HCl. Der Pharmacia Lettre, 2012;4(5) 1390-1400.

Photo
Pawde Manik Sambhaji
Corresponding author

Department of Pharmaceutics, School of Pharmacy, SRTMU, Nanded

Photo
Shiradhonkar Vikas Dashrath
Co-author

Department Pharmacology, Saraswati Intitute of Pharmacy Pangri, Nanded

Photo
Kendre Jayshri Marotirao
Co-author

Departmeent of Pharmaceutics, School Pharmacy, SRTMU,Nanded

Photo
Chaitnya Govind Bhatane
Co-author

PES Modern College of Pharmacy, Pune

Pawde Manik Sambhaji, Shiradhonkar Vikas Dashrath, Kendre Jayshri Marotirao, Chaitnya Govind Bhatane, Gastro Retentive Microspheres Based Drug Delivery: Formulation and Evaluation, Int. J. Sci. R. Tech., 2024, 1 (12), 313-317. https://doi.org/10.5281/zenodo.14571016

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