Formulation and Evaluation of Extended Release Oral Suspension of Metformin Hydrochloride
Dipali Patil, Shashikant Barhate, Manoj Bari, Shaikh Samir
Shri Suresh Dada Jain Institute of Pharmaceutical Education and Research, Jamner, Dist. Jalgaon.
*Corresponding Author E-mail: dipaliychinchole29@gmail.com
ABSTRACT:
The research scheme of formulation and evaluation of extended-release oral suspension of metformin hydrochloride with the objective to develop a stable, redispersible oral liquid suspension based on extended-release pellets to facilitate swallowing in patients with diabetes. Pellets were prepared by using Bed Coating During Sliding method with the Metformin hydrochloride used as antidiabetic drug and various polymers. Extended release was affected by the ethylcellulose coating of drug formulation used as coating agent, MCC, Lactose, PVP K-30 Prepared metformin hydrochloride pellets putted in to prepared sugar free syrup vehicle using polymers like Xanthan Gum as a suspending agent for uniform drug distribution, Sorbitol solution, Aspartame are artificial sweeteners, Sodium Citrate, Potassium sorbate, Methyl paraben. The formulation was optimized based on Design expert software and Central Composite Design was used for study. Drug and polymers were studied for compatibility and interaction study, carried out by FTIR and DSC and found to be compatible to each other. The Redispersibility, Sedimentation volume, Sedimentation rate, Rheological Study, Viscosity, Specific gravity, Particle Size, dissolution study and %Drug content of formulated batches was evaluated. All the results were within the acceptable pharmacopeial limits and were evaluated statistically by using one way ANOVA test for quadratic model. From the result, MET6 batch was observed optimized formulation because up to 8 hrs 85.25% drug was released. kinetic studies of the drug release for optimized formulation follows zero order kinetics.
KEYWORDS: Extended-Release Oral Drug Delivery System, Metformin Hydrochloride, Bed Coating During Sliding method, DoE.
1. INTRODUCTION:
In recent decades pharmaceutical industries are focusing on development of extended-release formulations due to its various advantages1.
A significant proportion of the populations such as paediatrics and geriatrics have difficulty in swallowing solid oral dosage forms and oral route of drug administration have wide acceptance up to 50-60% of total dosage forms2,3. Most oral dosage forms such as tablets and capsules are unsuitable for older people with swallowing difficulties. Capsules opening and tablet crushing are commonly used to overcome this problem4,5. An oral pharmaceutical suspension presents a novel means of circumventing the potential problems associated with the administration of such systems6. Extended release (ER) oral drug delivery System is the most preferred and expedient option over conventional oral dosage form7. The incorporation of extended-release technology in the oral suspension drug delivery system provides improvement in the rate and improvement the bioavaibility of some drugs particularly in pediatric class to reduce the toxicity due to overdose which often in conventional dosage form. higher patient compliance, maintain therapeutic effect and which reduce the dosing frequency of certain drugs by releasing the drug at slow rate and make the drug available over extended time period after oral administration8,9, Extended release dosage forms are allows at least a twofold reduction in dosage frequency as compared to that drug presented as an immediate release form10,11. Metformin is the first-line medication for the treatment of type 2 diabetes and is recommended for prevention or delay of diabetes onset in people at risk for developing type 2 diabetes12. The recommended starting dose is 5 ml (500mg) orally once daily with the evening meal2. Ethylcellulose is widely used coating polymer in pharmaceuticals in extended drug delivery system as it offers numerous advantages such as improved efficiency, reduced toxicity and improved patient compliance13. Then, these were formulated in to a suspension form, which can release the drug in a slow and controlled manner. The polymers used for pellets of drug adversely affects the rate of drug release from pellets. In the present work, Metformin hydrochloride coating of ethylcellulose was given to retard the drug release. Hence the present work is aimed at development and formulation of extended-release suspension with suitable concentration of ethylcellulose, xanthan gum in Metformin hydrochloride pellets. Developing extended-release oral formulations for drug at constant release rate has always been a challenge to the pharmaceutical technologist. The ideal drug delivery system should show a constant zero-order release rate and maintain the constant plasma concentrations1,3.
2. MATERIALS AND METHODS:
2.1 Materials:
2.2 Methods:
2.2.1 DoE Software used for study:
Design expert software was used for optimization of formulation in that Central composite design (CCD) was used for experimental design containing two independent variables Ethylcellulose (X1) and Xanthan Gum (X2) were investigated at three levels as low, medium and high given in table 1. While putting the values nine baches were generated by using central composite design. In that dependent variables were investigated in the response i.e %DR (Y1) and Viscosity (Y2). The statistical experimental design was evaluated through the analysis of variance (ANOVA) test using the Design Expert software (Version 13)14.
Table 1. Formulation Independent Variables, Actual Coded Values and their Levels of Central Composite Design
|
Actual Coded Value |
Levels |
|||||
|
-ᾱ |
Low |
Medium |
High |
+ᾱ |
||
|
Ethylcellulose |
X1 |
548.266 |
558 |
581.5 |
605 |
614.734 |
|
Xanthan Gum |
X2 |
2.4392 |
2.46 |
2.51 |
2.56 |
2.5807 |
2.2.2 Pre-formulation Studies:
1) Determination of UV Spectrum:
Metformin Hydrochloride Solution (10µg/ml) was prepared in phosphate buffer pH 1.2 and 6.8. This solution was scanned under a double-beam UV visible Spectrophotometer (Shimadzu1800) and the spectrum was recorded in the wavelength ranges between 200-400 nm.
2) Preparation of Calibration Curve of Metformin Hydrochloride:
Calibration curve of Metformin Hydrochloride in phosphate buffer pH. 1.2 and 6.8 was established by preparing different dilutions of the drug like 5, 10, 15, 20, and 25µg/ml from a stock solution of 10mg/100ml and taking the absorbance of these solutions was measured spectrophotometrically at λmax 233nm. Also, plotted the graph of absorbance of Metformin Hydrochloride against concentration in MS Excel and determined the slope and intercept.
3) Fourier Transform Infrared Spectroscopy (FTIR):
The FTIR studies were carried out using FTIR 1-S Affinity used to identify any drug and excipients interaction. The infrared spectra of Metformin Hydrochloride, and a mixture of drugs and excipients that examined using FTIR.
4) Differential Scanning Calorimetry (DSC):
2.2.3 Preparation of Extended-Release oral suspension of metformin hydrochloride2:
Preparation of Metformin hydrochloride pellets30 and coated with ethylcellulose for extended release of drug by using Bed coating during sliding method and incorporated in to prepared sugar free syrup vehicle using artificial sweeteners29, suspending agent, Buffering agent, antibacterial agent and antifungal agent.
Table 2: Formulation and Optimized Batches of Extended-Release Oral Suspension of Metformin Hydrochloride15:
|
Ingredient (mg/Suspension) |
Batches |
||||||||
|
MET1 |
MET2 |
MET3 |
MET4 |
MET5 |
MET6 |
MET7 |
MET8 |
MET9 |
|
|
500 |
500 |
500 |
500 |
500 |
500 |
500 |
500 |
500 |
|
|
35 |
35 |
35 |
35 |
35 |
35 |
35 |
35 |
35 |
|
|
Lactose |
35 |
35 |
35 |
35 |
35 |
35 |
35 |
35 |
35 |
|
PVP K -30 |
30 |
30 |
30 |
30 |
30 |
30 |
30 |
30 |
30 |
|
Distilled water |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
|
Ethylcellulose |
605 |
581.5 |
614.734 |
558 |
548.266 |
581.5 |
605 |
558 |
581.5 |
|
Ethanol |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
|
Xanthan Gum |
2.56 |
2.580 |
2.51 |
2.56 |
2.51 |
2.51 |
2.46 |
2.46 |
2.43929 |
|
0.44 |
0.42 |
0.49 |
0.44 |
0.49 |
0.49 |
0.54 |
0.54 |
0.57 |
|
|
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
1.25 |
|
|
Aspartame |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
|
75 |
75 |
75 |
75 |
75 |
75 |
75 |
75 |
75 |
|
|
100.00 |
100.00 |
100.00 |
100.00 |
100.00 |
100.00 |
100.00 |
100.00 |
100.00 |
|
|
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
|
|
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
5.00 |
|
|
Purified water |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
q.s. |
2.3 Evaluation Parameters of optimized Batches of Extended-Release Oral Suspension of Metformin Hydrochloride:
Evaluation of suspension: Evaluation of suspension carried out by checking following parameter16-23.
1. Appearance: Suspension was evaluated for colour, odour and taste.
2. pH: The pH determination study was carried out by using digital pH meter.
3. Viscosity: Viscosity of suspension was measured by using Brookfield viscometer having rotation per minute was 50Rpm and spindle no. 6126,32.
4. %Drug content determination: For the determination of drug content, a suspension containing 500mg metformin hydrochloride was filtered and the drug content was determined as mentioned previously.
5. Ease of Redispersibility: Ease of redispersibility was determined by allowing the suspension to settle in a stoppered measuring cylinder. The mouth of the cylinder was closed and was inverted through 180oC and the number of inversions necessary to restore a homogeneous suspension was determined3. The shakes required to redispersed is noted. As +++indicate excellent, ++indicate moderate, +indicate poor23.
6. Sedimentation time and sedimentation rate: The suspension was allowed to settle down for 24 hour and Sedimentation time (rate) as well as sedimentation volumes were determined. The sedimentation volume was calculated using the official formula as follow:
Sedimentation volume (Vs) = Hu/Ho
7. Rheological Study: The Rheological study was performed to know about the flow behavior of developed extended release suspension. Formulation containing xanthan gum when gave less viscous suspension leading to fast sedimentation. With increasing the quantity of xanthan gum to in the formulation, the prepared suspension was viscous and the particles were well suspended24,25.
8. In-Vitro Dissolution Study: The in vitro drug release forms the prepared suspension was performed by USP dissolution test apparatus i.e., paddle type at 100 rpm. In vitro study was carried out using 900ml of dissolution medium pre-warmed at 37±0.5oC. The pH of the buffer was 1.2 for first two hours 700 ml and volume make up to 900ml and pH raised up to pH 6.8 buffer for next six hours as dissolution media. A 5ml of aliquot was withdrawn at the specified time intervals from the dissolution medium and the samples were replaced by fresh dissolution medium then the samples were filtered and absorbency were measured at 233nm using UV/Visible spectrophotometer for Metformin Hydrochloride33
9. % DR= (Test Abs.)/(Std.Abs.) × (Std. dilution)/(Test dilution) × Purity/(Label claim)
10. Drug Content: The extended-release oral suspension of metformin hydrochloride from each formulation were powdered. The powder equivalent to 20mg of Metformin Hydrochloride was weighed and dissolved in phosphate buffer pH 6.8 in 100ml. From this suitable dilution was prepared and the solution was analyzed at 281nm using a UV double beam spectrophotometer (Shimadzu-1800) using pH 6.8 as blank13,23.
Drug Content (%) = Test Absorbance/Standard Absorbance × 100
11. Release Kinetic Model Study: Obtained data from in vitro drug release studies fitted to various kinetic models such as zero order, first order, Higuchi and Korsmeyer-Peppas to predict the drug release mechanism. The release rate constants (k), release exponent (n), and determination coefficients (R2) were calculated by means of a computer program (Microsoft Excel, 2019 version)26,27,28.
3. RESULT AND DISCUSSION:
3.1 Pre-formulation Parameters:
1. Determination of UV Spectrum and Calibration Curve of Metformin Hydrochloride:-
UV spectrum of Metformin Hydrochloride was presented in fig. 1 and the calibration curve shows the straight-line equation given in fig. 2.
Fig. 1: Wavelength Maxima of Metformin Hydrochloride in phosphate buffer pH. 1.2
Fig. 2: Wavelength Maxima of Metformin Hydrochloride in phosphate buffer pH. 6.8
Fig. 3: Calibration curve of Metformin Hydrochloride in Phosphate Buffer pH 1.2
Callibration curve of metformin HCl in pH 6.8 at 233 nm
Conc. (μg/ml)
Fig. 4: Calibration curve of Metformin Hydrochloride in Phosphate Buffer pH 6.8
2. Fourier Transform Infrared Spectroscopy (FTIR): FTIR results indicated when the IR spectrum of the Drug and polymers were compared with that of the mixture of drug and excipients to analyse drug excipient interaction given in fig.3
Fig. 5: FTIR Spectra of Metformin Hydrochloride
Fig. 6: FTIR Spectra of Ethylcellulose.
Fig. 7: FTIR Spectra of Drug and overlay
Fig. 8: FTIR Spectra of Xanthan Gum
3. Differential Scanning Calorimetry (DSC): was 224oC there was no difference between both DSC thermograph indicated that the melting point of the melting points i.e., indicated that no chemical and pure drug was 224°C and the drug-excipient mixture physical interaction was given in fig. 4.
Fig. 9: DSC Thermogram of Metformin Hydrochloride, Drug-Excipient Mixture of pellets and drug with excipients of syrup
Table 3: Evaluation Parameters of optimized Batches of Extended-Release Oral Suspension of Metformin Hydrochloride
|
Parameters |
Batches |
||||||||
|
MET1 |
MET2 |
MET3 |
MET4 |
MET5 |
MET6 |
MET7 |
MET8 |
MET9 |
|
|
Appearance |
Viscous liquid |
Viscous liquid |
Viscous liquid |
Viscous liquid |
Viscous liquid |
Viscous liquid |
Viscous liquid |
Viscous liquid |
Viscous liquid |
|
Taste |
Sweet |
Sweet |
Sweet |
Sweet |
Sweet |
Sweet |
Sweet |
Sweet |
Sweet |
|
Odour |
Pungent |
Pungent |
Pungent |
Pungent |
Pungent |
Pungent |
Pungent |
Pungent |
Pungent |
|
Color |
Light yellow |
Light yellow |
Light yellow |
Light yellow |
Light yellow |
Light yellow |
Light yellow |
Light yellow |
Light yellow |
|
pH |
4.5 |
4.0 |
4.1 |
4.6 |
4.7 |
4.4 |
5.0 |
4.8 |
5.0 |
|
Redispersibility |
+++ |
+++ |
+++ |
+++ |
+++ |
+++ |
+++ |
+++ |
+++ |
|
Sedimentation volume |
0.95 |
0.97 |
0.98 |
0.96 |
0.98 |
0.96 |
0.95 |
0.94 |
0.98 |
|
Sedimentation rate |
1/min |
1/min |
1/min |
1/min |
1/min |
1/min |
1/min |
1/min |
1/min |
|
Viscosity (Cps) |
1420 |
810 |
1340 |
760 |
540 |
840 |
1290 |
415 |
712 |
|
Specific gravity |
1.06 |
1.05 |
1.07 |
1.04 |
1.06 |
1.08 |
1.07 |
1.06 |
1.07 |
|
Particle Size (um) |
98-208 |
78-192 |
68-176 |
102-206 |
98.199 |
84-187 |
89-198 |
89-198 |
89-198 |
|
% DR |
80.51 |
80.51 |
80.51 |
80.51 |
80.51 |
80.51 |
80.51 |
80.51 |
80.51 |
3.2.1 Drug Release Kinetics Model Fitting of the Dissolution Data of Optimized Batches:
Fig. 10: In-Vitro Drug Release Study of Optimized Batches Generated by CCD (MET1-MET9)
Fig. 11: Zero Order Kinetics MET6 Batches
3.2.2 Optimization and Data Analysis:
Using the CCD method 9 batches of ER oral suspension of metformin hydrochloride were prepared by taking a different concentration of independent factors produced by DoE software and evaluated using various parameters like % drug release, Viscosity.
Table 4: Central Composite Design with Dependent Variables.
|
Batches |
Variable Level in Coded Form |
Dependent variables (Y) |
||
|
Factor 1 (X1) |
Factor 2 (X2) |
% Drug Release (Y1) |
Viscosity (Cps) (Y2) |
|
|
MET1 |
0 |
+α |
80.51 |
1316 |
|
MET2 |
-α |
0 |
84.25 |
1008 |
|
MET3 |
1 |
1 |
80.12 |
1340 |
|
MET4 |
1 |
0 |
88.3 |
649 |
|
MET5 |
0 |
-1 |
91.6 |
434 |
|
MET6 |
1 |
-1 |
85.25 |
840 |
|
MET7 |
0 |
0 |
82.12 |
1163 |
|
MET8 |
-1 |
1 |
90.45 |
489 |
|
MET9 |
-1 |
-1 |
86.9 |
791 |
Effect of Independent Variables on % Drug Release:
Following regression equation could describe the % Drug Release response,
%DR=+85.50+(-4.04) X1+(-0.9385) X2+(232.68) X1X2+(-0.1721) X12+(-18.769) X22
Concerning dissolution, the results of multiple linear regression analysis showed that the coefficients X1 bear negative sign and X2 bear a negative sign. It revealed that %drug release increases with decrease in EC and while %drug release decreases with increase in XG. Less amount of EC was expected to increase the % drug release. ANOVA was used to identify the significant effect. The result was found to be significant at that level of probability
Fig 12: 3D Response Surface Graph
Fig, 13: 3D Response Surface Graph
Effect of Independent Variables on Viscosity (Y2): Following regression equation could describe the Viscosity,
Viscosity =+85.50+(-4.04) X1+(-0.9385) X2+(232.68) X1X2+(-0.1721) X12+(-18.769) X22
Concerning dissolution, the results of multiple linear regression analysis showed that the coefficients X1 bear negative sign and X2 bear a negative sign. It revealed that % drug release increases with decrease in EC and while % drug release decreases with increase in XG. Less amount of EC was expected to increase the % drug release. ANOVA was used to identify the significant effect. The result was found to be significant at that level of probability (p<0.05).
Fig. 14: Response Surface Contour Graph
Fig. 15: 3-D Surface Graph
Table 5: Summary of Results of Analysis of Variance ANOVA for Quadratic Model:
Response 1: % Drug Release (Y1)
|
Source |
Sum of Squares |
DF |
Mean Square |
F-Value |
p-Value |
|
|
Model |
137.90 |
2 |
68.95 |
821.46 |
< 0.0001 |
Significant |
|
A-EC |
130.86 |
1 |
130.86 |
1558.98 |
< 0.0001 |
- |
|
B-XG |
7.05 |
1 |
7.05 |
83.94 |
< 0.0001 |
- |
|
Residual |
0.5036 |
6 |
0.0839 |
- |
- |
- |
|
Cor Total |
138.41 |
8 |
- |
- |
- |
- |
Table 6: Summary of Results of Analysis of Variance ANOVA for Quadratic Model: -
Response 2: % Viscosity (Y2)
|
Source |
Sum of Squares |
DF |
Mean Square |
F-Value |
p-Value |
|
|
Model |
9.076E+05 |
2 |
4.538E+05 |
692.97 |
< 0.0001 |
Significant |
|
A-EC |
8.595E+05 |
1 |
8.595E+05 |
1312.59 |
< 0.0001 |
- |
|
B-XG |
48032.07 |
1 |
48032.07 |
73.35 |
0.0001 |
- |
|
Residual |
3929.08 |
6 |
654.85 |
- |
- |
- |
|
Cor Total |
9.115E+05 |
8 |
- |
- |
- |
- |
4. CONCLUSION:
Extended-release oral suspension of metformin hydrochloride is a method to increase the duration of drug action being formulated without affecting onset of action. Extended-release suspension affected by coating the drug to be formulated as suspension by insoluble polymer coating. The polymer coating provides extended-release action and also masks the taste of the bitter drug. It can be concluded that the primary requirement of a successful extended-release oral suspension of metformin hydrochloride product focuses on increase patient compliance, preventing exposure to high drug concentrations, maximum absorption, reduction in side effects and improvement of bioavailability. The main advantage of ER suspension is decrease in dosing frequency. It involves initial release of active agent for achieving early onset of action which is then followed by its extended release for longer duration of action. This can be achieved by formulating extended-release oral suspension of metformin hydrochloride. From above result of the present study, it was conclusively demonstrated that the extended-release oral suspension of metformin hydrochloride formed successfully. The in-vitro drug release of Met 6 batch of formulation was best fitted with all specification of extended-release suspension was 85.25 % within 8 hrs and optimized formulation was follows which is exactly obeys the zero-order kinetic of drug release. Finally, it is concluded that the metformin hydrochloride suspension which is able to provide extended-release effect with great palatability and stability.
5. REFERENCES:
1. D Vamshidhar Reddy, Ambati Sambashiva Rao. A Review on Oral Extended-Release Technology. Research J. Pharm. and Tech. 2015; 8(10)
2. GM Roy. Crit Rev Food Sci Nutr. 1990; 29: 59-71.
3. Deepak Kaushik. Development of taste masked levofloxacin oral suspension using ion exchange resonates. Journal of Chemical and Pharmaceutical Research, 2016; 8(7): 385-394.
4. Liu, F., Ghaffur, A., Bains, J. and Hamdy, S. Acceptability of oral solid medicines in older adults with and without dysphagia: a nested pilot validation questionnaire based observational study. Int J Pharm. 2016; 512: 374-381.
5. Kavil Patel, Valentyn Mohylyuk, Darragh Murnane, Craig Richardson, Fang Liu. Development of multi-dose oral sustained release suspensions for older patients with dysphagia. University of Hertfordshire., September 2018.
6. Devrim B. Bozkir A and Canefe K. Formulation and evaluation of reconstitutable suspension containing ibuprofen-loaded eudragit microshepers. Acta poloniae harmaceutca- Drug Research. 2011; 68: 593-599.
7. Sarika S. Lokhande, Phalke N.N. and Badadare S.S. A Review on sustained Release technology. Would Journal of Pharmaceutical and Medical Research, 2019; 11: 60-65.
8. Smith HA, Evanson RV and Sperandio GJ. The development of a liquid antihistaminic preparation with sustained release properties. J Am Pharm Assoc Am Pharm Assoc. 1960; 49: 94-97.
9. Moldenhauner MG and Nairen JG. Formulation parameters affecting the preparation and properties of microencapsulated ion exchange resins containing theophylline J. Pharm Sci. 1990; 79: 659-9766.
10. Alfanso R Gennaro, Remington’s The Science and Practice of Pharmacy, 20th Edition 200: 903-929.
11. Manish R. Bhise, Mahesh B. Narkhede, Sumedh P. Mohod, Amol H. Mohade. Development and evaluation of extended release Ambroxol HCl and Guaifenesin suspension; Research J. Pharm. And Tech. 2012; 5(1).
12. Satterwhite LE. Metformin Extended-Release Oral Solution. National Centre for Biotechnology information. 2021; 39(2).
13. Nicolas G, Mare P, Bernard M. et. al., Study of release kinetics of small and high molecular weight substances dispersed into spray dried microspheres. K. Controlled Release. 2002; 84: 125-135.
14. N. K. Jain, Pharmaceutical Product Development, 2nd Edition, CBS Publication and Distributed PVP. LTD; New Dheli, 393-395.
15. Chandan S. Design and evaluation of Ethyl Cellulose Based Matrix Tablets of Ibuprofen with pH Modulated Release Kinetics. Indian Journal of Pharmaceutical Sciences. 2008; 5(70): 596-602.
16. Bora, D., Borude, P., Bhise, K., Formulation and Evaluation of Self microemulsifying drug delivery systems of low solubility drug for enhanced solubility and dissolution. International Journal of Pharmaceutical Innovation. 2-19.
17. Kulkarni, A. P., Shahnawaz, M., Zaheer, Z., Dehghan, M., H. G. Development and Validation of a Dissolution Method for Pioglitazone Tablets. Dissolution Technologies. 2012; 36-45.
18. Van Zwet AA, de Boer WA, Schneeberger Pam, Weel J, Jansz AR, Thijs JC. Prevalence of primary Helicobacter pylori resistance to metronidazole and clarithromycin in the Netherlands. Eur J Clin Microbial Infect Dis. 1996; 15:861-864.
19. Akiram E. I, Ibrahim K.E, studies on the photochemical decomposition of Metronidazole, International Journal of Pharmaceutics. 1991; 261-264.
20. Boner A. Sustained release suspension of theophylline. Int J Clin Pharma Res. 2000; 5: 345-50.
21. Kadam A, Sakarkar D, Kawatikwar P. Development and Evaluation of oral controlled release Suspension of chlorpheniramine, Int J Pharma Sci. 2008; 20 (5):531-534.
22. Ms. Aarti Darode, Mrs. Namita S. Girhepunje, Mr. Nilesh Mahajan, Mr. Nitin G. Dumore. Formulation Development and Evaluation of Oral Sustained Release Suspension containing Antidiarrheal Drug. Research J. Pharm. And Tech. 2019; 12(10): 1-5.
23. Patil P. D., Desai S, R, Disouza J. I. Stability analysis and quantitative evaluation of metronidazole suspension. Indian Journal of Pharmaceutical and Biological Research. 2016; 4(3): 5-14.
24. Mhadgut A and Nalawade VV: Oral extended-release dry suspension of paracetamol loaded microspheres. Int J Pharm Sci Res. 2017; 8(7): 2922-31. doi: 10.13040/ IJPSR.0975-8232.8(7).2922-31.
25. Dr. Bhise S. B., Dr. Dias R. J., Dr. Dhawale S. C., Shri. Mali K. K. 'Laboratory Manual of Biopharmaceutics and Pharmacokinetics'. Trinity Publication; 22,23.
26. Suhagia BN, Shah SA, Patel HM, Doshi KR, Parmar VK. Spectrophotometric estimation of Roxithromycin in tablet dosage form. Indian Journal of Pharmaceutics. 2006; 68(4): 543-546.
27. Abhay N, Padalkar, Sadhana R Shahi, Yoganand K, Udavant, Ravindra J Salunke et al. An approach towards taste abatement of Roxithromycin. International Journal of Pharmaceutical Research and Development. 2009; 7(1).
28. D Jain; S Verma; SB Shukla; AP Jain; P Jain; P Yadav. J Chem Pharm Res. 2010; 2(4): 935-978.
29. Afaque Raza Mehboob Ansari, Review on artificial sweeteners used in formulation of sugar free syrups, International Journal of Advances in Pharmaceutics, Volume 4 (2)2015.
30. Umme Hanee, Venkatesh DP, Pelletization – A new horizon, International Journal of Creative Research Thoughts. 2020: 2320-28820.
31. Shete AS, Yadav AV, Dabke AP, Sakhare SS. Formulation and evaluation of hydrotropic solubilisation-based suspensions of Griseofulvin. International Journal of Pharma Sciences and Research. 2010; 1(1): 51-57.
32. Suthar AM, Patel MM. Development of taste masked liquid formulation of Tinidazole using Ion-Exchange resin complexes. Journal of Pharmaceutical Science and Technology. 2010; 2(9): 303-307.
33. Umesh V. Bankar, Pharmaceutical Dissolution Testing, Informa Health Care, New Yourk London, Vol49. 280-285.
Received on 30.09.2023 Modified on 17.11.2023
Accepted on 25.12.2023 ©AandV Publications All Right Reserved
Res. J. Pharma. Dosage Forms and Tech.2024; 16(1):6-12.
DOI: 10.52711/0975-4377.2024.00002