Formulation Development and Evaluation of Multiple Unit Pellet System of Tamsulosin Hydrochloride

 

Gavaskar Basani¹*, Dr. Madhusudan Rao Yamsani², Ramya Sri Sura³

¹Department of Pharmacy, Jawaharlal Nehru Technological University, Kukatpally,

Hyderabad, Telangana, 500085, India.

²Department of Pharmaceutics, Vaagdevi College of Pharmacy, Warangal, Telangana, 506005, India.

³Department of Pharmacy, University College of Technology,

Osmania University, Hyderabad, Telangana, 500007, India.

 

ABSTRACT:

The aim of current work was to grow extended release multiple unit pellets of Tamsulosin Hydrochloride, is an alpha-blocker, used for the healing of the symptoms of a prostate gland condition called BPH (benign prostatic hyperplasia) by extrusion- spheronization (E/S) and solution/suspension layering (S/S) method. In the Extrusion-Spheronization, A ratio of 75:25, 67:33, 64:36 Tamsulosin Hydrochloride and Microcrystalline cellulose were mixed for making drug pellets and extended release (ER) coating was performed in fluidized bed processor (FBP) by solution/suspension layering with Ethyl cellulose (aqueous. dispersion, 4 cps and 7 cps) and Hypromellose (5cps) with different ratios % weight buildups accordingly. In the Solution/suspension layering (S/S) method, Tamsulosin Hydrochloride drug pellets were prepared by layering onto MCC spheres in FBP. These drug pellets were further coated for extended release with HPMC, 5cps and EC, 7cps. In drug coating stage, drug and different binder (Hypromellose, 5 cps) concentrations 8, 10, 12, 14 mg/unit were coated onto the cores for optimization of binder concentration. The weight of MCC spheres were optimized for further formulations. For all the drug coated pellets, ER coating was given with EC, 7cps and HPMC, 5 cps at a coating level of 8% weight by weight. In the extrusion- spheronization (E/S) Optimization of Drug pellets: Among the trials TD3 (Tamsulosin HCl and MCC) showed good mechanical strength with better yield due to increased MCC concentration. Optimization of Extended Release Coating: Optimized TD3 drug pellets were coated with ER coating using water insoluble polymer (Aq.EC 25% dispersion/ EC, 4cps/ EC, 7cps) and water soluble polymer (HPMC, 5cps). Among these polymers, extended release coating was optimized (TD3E14) with the combination of EC, 7cps and HPMC, 5cps at 8% weight build up. In the Solution/Suspension layering: Optimization of binder concentration in drug coating stage: HPMC, 5cps with 12 mg/unit for TF7 was optimized based on %yield. Optimization of MCC spheres in drug coating stage in formulation of ER pellets with different weight drug pellets: The weight of MCC spheres (160, 170, 180, 190 mg/unit) used in the drug coating stage with binder HPMC, 5cps (12 mg/unit). These drug pellets were given with ER coating at 8% weight buildup by using EC, 7cps and HPMC, 5cps. Among these trials, TF7E7 was optimized.  Based on the investigations of the present study, conclusions was. formulating low dose, high soluble, BCS class I drug- Tamsulosin Hydrochloride ER formulation by extrusion-spheronization showed flexibility for batch processing and cost effectiveness while solution/suspension layering was process feasible but time consuming due to high drug loading.

 

 

INTRODUCTION:

Pelletization is one of the the majority promising techniques for the multi particulate drug delivery systems^1,2,3. Pellets are of about 0.2-2.0 mm mean particle diameter, small, free flowing, spherical/ semi spherical agglomerates attained from assorted starting ingredients of fine powder(s)/granule(s) of bulk drug(s) and/or excipient(s) employing different pelletization techniques^4,5. Multiparticulate drug release systems are the utmost accepted and widely used prescribed amount form as they propose so many benefits over unit measured quantity forms like superior bioavailability because of improved surface area, abridged inter subject variation and transportation and reduced odds of dose dumping^2,6. The attention in pellets as dosage forms (filled into hard gelatine capsules or squashed into disintegrating tablets) has been escalating incessantly^7,8. Tamsulosin hydrochloride, a highly selective alpha 1A-adrendoreceptor antagonist that has been used for the dealing of poorer urinary tract symptoms evocative of benign prostatic hyperplasia^9,10. A enhanced preparation of Tamsulosin hydrochloride involves extended release that offers more stable plasma profiles and thus reduces any adverse effects¹¹. The objective of this study was to establish a novel, simple, and flexible 2 methods Extrusion-Spheronization (E/S) and solution/suspension layering (S/S) of preparing extended-release pellets was tried to optimize the best fit process for Tamsulosin.

 

MATERIALS:

Tamsulosin Hydrochloride was procured from Intas Pharmaceuticals Limited, Provided by Sura Labs, Dilsukhnagar. Microcrystalline Cellulose (MCC), MCC spheres, Ethylcellulose (EC)- 4 cps, 7 cps, Hypromellose (HPMC) - 5 cps, Isopropyl Alcohol (IPA) were purchased from S.D Fine chemicals, Mumbai.

 

METHODOLOGY:

Preparation of Extended release pellets of Tamsulosin Hydrochloride HCl-Method A: Extrusion-Spheronization:

 

Table 1: Optimization of Tamsulosin HCl Drug Pellets

Quantity →	mg/unit
Ingredients ↓	TD1	TD2	TD3
Tamsulosin HCl	0.2	0.2	0.2
MCC (Avicel PH 101)	153.5	180	190
Purified water**	124	138.3	144
% Water uptake to the dry mix weight	53.49	53.54	53.58
Total weight of drug pellets	153.7	180.2	190.2

** It will not appear in final product except in traces.

 

Table 2: Optimization of Tamsulosin HCL Extended release coating polymer

Formulation code	%weight build up onto drug pellets (%w/w) ↓	Ingredients ↓
		Drug Pellets	Ethylcellulose12  (Aqueous dispersion 25%) *	Ethylcellulose,  4 cps	Ethylcellulose, 7 cps	Hypromellose, 5 cps	Isopropyl Alcohol**	Purified water**	Total weight of ER pellets	% w/w solids in solution/ suspension
TD3E1	7.5%	190.2	67.6 (16.9)	-	-	1.85	160	16.25	208.95	7.63
TD3E2	15%	190.2	135.20 (33.8)	-	-	3.7	320	32.5	227.7	7.63
TD3E3	7.5%	190.2	-	16.9	-	1.85	160	66.95	208.95	7.63
TD3E4	15%	190.2	-	33.8	-	3.7	320	133.9	227.7	7.63
TD3E5	7.5%	190.2	-	-	16.9	1.85	160	66.95	208.95	7.63
TD3E6	15%	190.2	-	-	33.8	3.7	320	133.9	227.7	7.63
TD3E7	5%	190.2	-	-	10	2.5	95	31.67	202.7	9.0
TD3E8	6%	190.2	-	-	12	3	114	38	205.2	9.0
TD3E9	7%	190.2	-	-	14	3.5	133	44.33	207.7	9.0
TD3E10	8%	190.2	-	-	16	4	152	50.66	210.2	9.0
TD3E11	5%	190.2	-	-	9.375	3.125	106.29	34.7	202.7	8.14
TD3E12	6%	190.2	-	-	11.25	3.75	127.55	41.64	205.2	8.14
TD3E13	7%	190.2	-	-	13.125	4.375	148.81	48.58	207.7	8.14
TD3E14	8%	190.2	-	-	15	5	170.07	55.52	210.2	8.14

* contains 25% w/w solid content

** It will not appear in final product except in traces

 

Method B: Solution/Suspension Layering¹³:

Tamsulosin HCl drug pellets were prepared by layering on to MCC spheres in a fluid bed processor¹⁴.

 

Table 3: Tamsulosin HCl drug coating stage and formulation of ER pellets

Quantity→	mg/unit
Optimization of binder concentration in Tamsulosin HCl drug coating stage
Ingredients↓	TF1	TF2	TF3	TF4	TF5	TF6	TF7	TF8
Microcrystalline Cellulose Spheres15 (CP708)	150	150	150	150	160	170	180	190
Tamsulosin HCl	0.2	0.2	0.2	0.2	0.2	0.2	0.2	0.2
Hypromellose16, 5 cps	8	10	12	14	12	12	12	12
Purified water**	694	702	710	710	505	602	602	710
Total weight of drug pellets	158.2	160.2	162.2	164.2	172.2	182.2	192.2	202.2
% w/w solids in solution/suspension	19.49	19.5	19.5	19.68	25.41	22.22	22.22	19.5
Formulation of ER pellets with different binder concentration drug pellets
Quantity →	mg/unit
Ingredients↓	TF1E1	TF2E2	TF3E3	TF4E4	TF5E5	TF6E6	TF7E7	TF8E8
Drug pellets	158.2	160.2	162.2	164.2	172.2	182.2	192.2	202.2
Ethylcellulose, 7 cps	13.08	13.2	13.32	13.44	13.92	14.52	15.12	15.72
Hypromellose, 5 cps	4.36	4.4	4.44	4.48	4.64	4.84	5.04	5.24
Isopropyl Alcohol**	146.67	148.05	149.06	150.44	155.96	162.48	169.38	176.28
Purified water**	48.89	49.35	49.69	50.15	52	54.16	56.46	58.76
Total weight of ER pellets	175.64	177.6	179.96	182.12	190.76	201.56	212.36	223.16
% w/w solids in solution/suspension	8.19	8.19	8.2	8.2	8.19	8.2	8.2	8.19

** It will not appear in final product except in traces.

EC:HPMC→75:25

% Weight build up (%w/w)→ 8%

 

Evaluation Parameters:

Characterization of pellets and capsules:

The characterization of pellets was evaluated as per USP, IP standards^17,18

 

In vitro drug release studies:

In vitro dissolution testing of solid dosage forms is the most frequently used biopharmaceutical test method in formulation development. Purpose of dissolution testing in research and development includes: obtaining a predefined target release profile.And the procedure as per USP, IP standards.

 

Scanning Electron Microscopy (SEM)¹⁹:

SEM of prepared coated and uncoated pellets was performed for studying pellet surface morphology.

 

Accelerated Stability Studies (AST):

The purpose of stability testing is to allow the establishment of recommended storage conditions and shelf lives at ambient conditions.^20-22 AST of the best fit formulations of the drug products were done at the end of 1^st, 2^nd, 3^rd months.

 

In vivo Studies:

Twelve healthy male rabbits weighing 1.5±0.2 kg were stored in large, spacious, and ventilated polyacrylic cages in well hygienic conditions. Four groups, each of 3 rabbits were selected for the present study. Control, Standard (Tamsulosin Hydrochloride API 0.2 mg), Test (Tamsulosin Delayed Release Capsule- TD3E14), Marketed Product groups (Urimax Delayed Release Capsule 0.2 mg). The vein of rabbit marginal ear vein was punctured with Syringe and blood sample was collected pre-filled with 20 µL of 10 % disodium EDTA. Mixed well and centrifuged the blood at 3200 rpm for 5 min. The supernatant layer of plasma 50 µL of plasma sample was used for analysis. Same procedure was used for blank plasma collection as well as drug treated rabbits at time points 0, 0.25, 0.5, 1, 2, 4, 6, 12, 24 hrs and analysis was carried out by HPLC method.

 

RESULTS AND DISCUSSION:

Tamsulosin Hydrochloride Calbration curve:

In pH 1.2 buffer at 320 nm and pH 6.8 phosphate buffer at 320 nm, calibration curves were plotted. The regression coefficient was found to be 0.998, 0.999 which indicates a linearity. Hence beer - lamberts law was obeyed.

 

EVALUATIONPARAMETERS:

Table 4: Characterization of Tamsulosin ER pellets and pellets in capsule prepared by E/S, S/S

Tamsulosin ER pellets and pellets in capsule prepared by E/S
Formulation	%w/w ER coating	% Yield	BD (g/mL)	TD (g/mL)	CI (%)	HR	% Friability	Average weight	% drug content
TD3E1	7.5	92.9	0.58±0.01	0.69±0.05	15.94±0.01	1.18±0.04	0.16± 0.95	344.75	98.2 ±0.91
TD3E2	15	95.5	0.48±0.09	0.57±0.05	15.78±0.05	1.18±0.06	0.18± 0.34	363.50	97.5 ±0.02
TD3E3	7.5	94.2	0.54±0.02	0.65±0.04	16.92±0.04	1.2±0.07	0.25± 0.11	344.75	97.8 ±0.24
TD3E4	15	92.7	0.54±0.05	0.64±0.04	15.62±0.05	1.18±0.08	0.39± 0.21	363.50	97.2 ±0.15
TD3E5	7.5	95.0	0.53±0.02	0.65±0.05	18.46±0.09	1.22±0.07	0.19± 0.32	344.75	98.5 ±0.31
TD3E6	15	91.8	0.56±0.03	0.66±0.02	15.15±0.02	1.17±0.05	0.26± 0.98	363.50	98.1 ±0.67
TD3E7	5	93.6	0.49±0.05	0.57±0.06	14.03±0.01	1.16±0.02	0.15± 0.52	338.5	97.2 ±0.59
TD3E8	6	94.7	0.56±0.04	0.67±0.08	16.41±0.00	1.19±0.05	0.20± 0.75	341.00	97.6 ±0.44
TD3E9	7	93.9	0.52±0.09	0.64±0.02	18.75±0.09	1.23±0.06	0.31± 0.42	343.5	98.2 ±0.65
TD3E10	8	94.2	0.55±0.001	0.62±0.005	11.29±0.10	1.13±0.011	0.42± 0.69	346.00	97.3 ±0.29
TD3E11	5	95.5	0.57±0.003	0.64±0.003	10.94±0.07	1.12±0.007	0.32± 0.87	338.50	98.3 ±0.73
TD3E12	6	94.1	0.59±0.004	0.69±0.004	11.94±0.09	1.14±0.011	0.36± 0.45	341.00	98.7 ±0.55
TD3E13	7	95.3	0.61±0.004	0.72±0.005	15.28±0.28	1.18±0.010	0.96± 0.58	343.50	97.9 ±0.29
TD3E14	8	93.4	0.52±0.003	0.58±0.002	10.34±0.09	1.12±0.009	0.14± 0.69	346.00	99.2 ±0.54
Tamsulosin ER pellets and pellets in capsules prepared by S/S
Formulation	%w/w ER coating	% Yield	BD (g/mL)	TD (g/mL)	CI (%)	HR	% Friability	Average Weight	% Drug content
TF1E1	8	98.2	0.46±0.020	0.51± 0.027	11.56±0.7	1.13±0.03	0.03± 0.10	311.44	98.3 ±0.98
TF2E2	8	96.5	0.42±0.040	0.54± 0.012	15.97±0.5	1.17±0.07	0.10± 0.34	313.60	99.4 ±0.14
TF3E3	8	99.2	0.47±0.017	0.56± 0.023	12.88±0.5	1.10±0.01	0.16± 0.12	315.76	97.3 ±0.25
TF4E4	8	97.9	0.41±0.034	0.49± 0.010	13.62±0.6	1.09±0.02	0.10± 0.45	317.92	98.9 ±0.12
TF5E5	8	99.2	0.49±0.030	0.53± 0.030	14.44±0.7	1.18±0.05	0.12± 0.39	326.56	98.2 ±0.24
TF6E6	8	98.0	0.44±0.015	0.49± 0.021	17.03±0.4	1.06±0.06	0.15± 0.17	337.36	99.5 ±0.82
TF7E7	8	99.6	0.46±0.022	0.55± 0.022	16.36±0.5	1.19±0.05	0.11± 0.34	348.16	98.4 ±0.62
TF8E8	8	99.4	0.42±0.010	0.50± 0.019	16.60±0.7	1.19±0.02	0.14± 0.13	358.96	97.9 ±0.70

 

In vitro Drug Release Studies:

Table 5: Dissolution Profiles of Tamsulosin Hydrochloride ER Capsules 0.2 mg prepared by Extrusion-Spheronization¹⁵ (TD3E1-TD3E14) and prepared by Solution/Suspension Layering (TF1E1-TF1E8)

Tamsulosin Hydrochloride ER Capsules prepared by Extrusion-Spheronization (TD3E1- TD3E14)
Formulations	Time (Hours)
	0	1.5	4	8	14	24
Marketed product	0	23	52	73	85	99
TD3E1	0	98	100	101	102	103
TD3E2	0	95	98	99	100	101
TD3E3	0	45	78	98	100	102
TD3E4	0	32	60	84	96	100
TD3E5	0	21	49	60	71	76
TD3E6	0	8	28	36	48	57
TD3E7	0	15	43	59	80	86
TD3E8	0	10	35	43	62	75
TD3E9	0	23	52	81	90	100
TD3E10	0	17	50	65	79	96
TD3E11	0	53	90	100	101	104
TD3E12	0	42	80	92	100	105
TD3E13	0	18	62	85	102	106
TD3E14	0	20	59	76	90	100
Tamsulosin Hydrochloride ER Capsules prepared by Solution/Suspension Layering (TF1E1-TF1E8)
Formulations	Time (Hours)
	0	1.5	4	8	14	24
Marketed Product	0	23	52	73	85	99
TF1E1	0	6	30	49	73	90
TF1E2	0	8	29	53	75	94
TF1E3	0	12	33	52	71	91
TF1E4	0	10	26	53	80	96
TF5E5	0	8	30	56	81	96
TF6E6	0	18	39	62	86	99
TF7E7	0	26	51	77	91	100
TF8E8	0	30	55	85	90	100

 

Figure 1: Comparative dissolution profile of Tamsulosin Hydrochloride marketed product, TD3E1-TD3E14 and TF1E1-TF1E4,TF5E5-TF8

 

TD3E11 (5% w/w) at 1.5 hours more than 50%; TD3E12, TD3E13 (6%, 7% w/w) at 14 hours 100% was noticed. The formulation TD3E14 at a coating level of 8% w/w showed better retarding nature due to the effect of the chosen polymer combination, ratio and weight buildup and was in compliance with USP limits and marketed product. Hence PD3E14 was considered as best one for formulating ER pellets prepared by extrusion -spheronization of the selected model drug.

Formulations TF6E6, TF7E7, TF8E8 prepared by solution/suspension layered technique dissolution profiles were evaluated. The drug release profiles of the formulation TF6E6 was slower, TF8E8 was faster and TF7E7 comply compared with the marketed product. Based on these results, formulation TF7E7 with 80 mg/unit MCC spheres was finalized.

 

Scanning Electron Microscopy (SEM):

SEM results of optimized formulations of Tamsulosin Hydrochloride ER Pellets, uniformity in size and sphericity, and porosity was minimal were shown in figure.

 

Figure 2: SEM analysis of Tamsulosin Hydrochloride ER Pellets prepared by extrusion-spheronization and solution/suspension layering (a) TD3E14 (b) TF7E7

 

Accelerated Stability Studies (AST) Results of AST showed that the optimized formulations of Tamsulosin Hydrochloride (TD3E14, TF7E7); were stable at 40±2°C/75±5% RH for 3 months. Hence these formulations as well as the process were considered as robust²³.

 

Table 6: AST results of Tamsulosin HCl ER Capsules 0.2 mg (TD3E14-8%w/w) Prepared by Extrusion-Spheronization and (TF7E7-8%w/w) Prepared by Solution/suspension Layering

Extrusion-Spheronization
Test parameter	Initial	1st month		2nd month	3rd month
Assay (% w/w)	99.3	98.7		98.8	98.6
Dissolution Profile (cumulative % drug release)
1.5 hrs	16	18		19	19
4 hrs	51	53		56	52
8 hrs	70	72		75	76
14 hrs	89	92		94	98
24 hrs	98	99		100	98
Solution/suspension Layering
Test parameter	Initial	1st month		2nd month	3rd month
Assay (% w/w)	99.5	99.3		99.6	99.2
Dissolution Profile (cumulative % drug release)
1.5 hrs	20	21	24		19
4 hrs	44	49	50		55
8 hrs	76	78	73		75
14 hrs	91	93	96		98
24 hrs	99	100	100		98

 

In vivo Studies:

The selected drug formulation Tamsulosin Hydrochloride DR Capsules 0.2 mg (TD3E14) was evaluated for its pharmacokinetics in animal model rabbit.

 

Table 7: Estimation of Pharmacokinetics parameters in rabbit

Time (hrs)	Mean Concentration (mg/mL)
	Standard (Tamsulosin Hydrochloride)	Test product (TD3E14)	Marketed product
0.00	0.00	0.00	0.00
0.25	59.15	14.9	10.22
0.50	77.9	49.5	30.51
1.00	110.2	99.7	81.64
2.00	138.0	123.4	106.05
4.00	175.3	135.5	154.17
6.00	252.6	240.4	210.12
12.00	104.2	98.5	55.19
24.00	45.11	22.23	11.33
Cmax (mg/mL)	252.6	240.4	200.12
Tmax (hrs)	6	6	6
AUMCt (mg.h/mL)	25729.19	21147.90	14254.01
AUCt (mg.h/mL)	2903.11	2534.64	1947.81

 

Figure 3: Comparative graph of Plasma Concentration Vs Time

 

CONCLUSION:

Extended release pellets were formulated with ER polymeric in actives that reduces frequency of dosing and enhances drug efficacy by releasing the drug at the required site and offers consistent delivery for 24 hours. Polymeric mixtures, mainly water insoluble-water permeable plus water swellable-water soluble cellulose derivatives are helpful in controlling the drug release characteristics of dosage forms. ER coating comprising hydrophilic-hydrophobic polymer derivatives is being researched extensively as this approach of coating controls the drug release by conjoined polymer drift i.e., swelling, erosion and diffusion via hydrated gel. The present study results summarized that Ethylcellulose, 7 cps and Hypromellose, 5 cps in the ratio 75:25 was qualitatively coherent for the preparation of pellets of Tamsulosin HCl. In addition to, for formulating low dose drugs, extrusion- spheronization²⁴ is considered as best fit process. TD3E14 formulation was considered as optimized formulation.

 

АCKNOWLEDGEMENT:

Thе Authors arе thankful to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе nеcеssary facilitiеs for thе rеsеarch work.

 

REFERENCES:

1.      Vogelson CT. Modern Drug Discovery. Advances in drug delivery systems; 4th ed. 2001: 49–52.

2.      Bechgaard H, Nielsen GH. Controlled- Release Multiple-Units and Single-Unit Doses a Literature Review. Drug Dev Ind Pharm 1978; 1: 53-67. doi.org/10.3109/03639047809055639.

3.      Kishore Manoharan, Navya Ajitkumar Bhaskaran, Lalit Kumar. Pellets and Techniques of Pelletization. Research J. Pharm. and Tech. 2019; 12(12): 6157-64. doi.org/ 10.5958/0974-360X.2019.01070.9

4.      Ghebre Sellassie - I., Pellets: A General Overview, Pharmaceutical Pelletization Technology.1989; 241-65.

5.      Susmit S. Diggikar, Tanaji D. Nandgude, Sushilkumar S. Poddar. Formulation of Modified Release Pellets of Montelukast Sodium. Research J. Pharm. and Tech. 2018; 11(1): 31-7. doi.org/ 10.5958/ 0974-360X.2018.00006.9.

6.      Sapkal SR, Jaiswal SB, Chandewar AV, Gaikwad SB, Pathan AM. Pellets as Controlled Release Drug Delivery System: A Review. Research J. Pharma. Dosage Forms and Tech. 2009; 1(3): 179-83. Available on: https://rjpdft.com/ HTMLPaper.aspx?Journal=Research%20Journal%20of%20Pharmaceutical%20Dosage%20Forms%20and%20Technology;PID=2009-1-3-2.

7.      Naik JB, Mokale VJ, More DB, Bari MM, Chavhan RB, More BB. Failure of Functionality of Coated Pellets into Tablets – Problems and Solutions. Research J. Pharm. and Tech. 2011; 4 (1): 43-6. Available on: https://rjptonline.org/ AbstractView.aspx?PID=2011-4-1-28.

8.      Nanda RK, Gaikwad J, Prakash A. Simultaneous Spectrophotometric Estimation of Tamsulosin in Pharmaceutical Dosage Form. Asian J. Research Chem. 2009; 2(1): 63-5. Available on: https://ajrconline.org/ AbstractView.aspx?PID=2009-2-1-17.

9.      Mihir K Raval, Riddhi V Ramani, and Navin R Sheth. Formulation and evaluation of sustained release enteric-coated pellets of budesonide for intestinal delivery. Int J Pharm Investig. 2013; 3(4): 203–11. doi.org/ 10.4103/2230-973X.121294.

10.   O'Leary MP. Tamsulosin: current clinical experience. Urology 2001; 58: 42-8.

11.   Xiong Zhang, Xing Tang, and Rui Yang. Development of a Tamsulosin Hydrochloride Controlled-Release Capsule Consisting of Two Different Coated Pellets. Drug Development and Industrial Pharmacy. 2009; 35: 26–33. doi.org/10.1080/ 03639040802144203.

12.   Y. Surkha, P. Venugopalaiah, K. Gnan Prakash, M. Gobinath. Design and Characterization of Enteric Coated Delayed Release Pellets of Rabeprazole Sodium. Research J. Pharm. and Tech. 2013; 6(12): 1380-86. Available on: https://rjptonline.org/ AbstractView.aspx?PID=2013-6-12-5.

13.   D. V. Madat, M. C. Gohel, A.Ramkishan. Development of Venlafaxine Hydrochloride Controlled Release Pellets Prepared Employing the Blend of Ethyl Cellulose and Polyethylene Oxide. Research J. Pharm. and Tech. 2012; 5(10): 1289-92. Available on: https://rjptonline.org/AbstractView.aspx?PID=2012-5-10-40.

14.   Rupam A. Wagh, Rajendra K. Surawase. Formulation and Development of Sustained Release Pellets of Nifedipine by Fluidized Bed Processor. Research J. Pharm. and Tech. 2020; 13(4):1757-61. doi.org/ 10.5958/0974-360X.2020.00317.0

15.   Sangram M. Patil, Rakesh V. Mishra, Satish V. Shirolkar. Development and Evaluation of Sustain Release Simvastatin Pellets. Research J. Pharm. and Tech. 2017; 10(8): 2467-73. doi.org/ 10.5958/0974-360X.2017.00436.X

16.   Tushar M. Patel, Mukesh C. Gohel. Development of Extended Release Pellets of Quetiapine Fumarate by using HPMC and Eudragit RSPO. Research J. Pharm. and Tech. 2014; 7(7): 771-5. Available on: https://rjptonline.org/ AbstractView.aspx?PID=2014-7-7-17.

17.   United States Pharmacopeia: <616> Bulk Density and Tapped Density of Powders, USP 32, 226.

18.   Indian pharmacopoeia, (1996) Vol I & II, The controller of publications, Delhi, 137-8.

19.   G.T. Kulkarni, B. Gowthamarajan, B. Suresh, Stability testing of pharmaceutical products-An overview, Ind. J Pharm. Educ. 2004; 38(4): 194-8.

20.   Stability testing of active pharmaceutical ingredients and finished pharmaceutical products, Annexure 2, WHO Technical Report Series, 2009; 953.

21.   John Lennon, Handbook of Stability Testing in Pharmaceutical: Development Regulations, Methodologies and Best Practices, Kim Huynh-Ba, Pharmalytik Newark, Delaware, 2008.

22.   Thorat Punam, Warad Shubhangi, Solunke Rahul, Ashok Sargar, Anagha Bhujbal, Asha Shinde. Stability Study of Dosage Form: An Innovative Step, World Journal of Pharmacy and Pharmaceutical Sciences. 2010; 3(2): 1031-50. Available on: https:// www.wjpps.com/Wjpps_controller/abstract_id/798.

23.   Viswanadham Manasa, K.Vanitha, M. Venkataswamy, P. Prabhakar, Alluri Ramesh. Formulation and Evaluation of Aqueous Enteric Coated Delayed Release Omeprazole Pellets. Res. J. Pharm. Dosage Form. & Tech. 2016; 8(1): 01-4. doi.org/ 10.5958/0975-4377.2016.00002.1

24.   Hardik B. Rana, Mukesh C. Gohel, Mansi S. Dholakia, Tejal R. Gandh, Abdelwahab Omri, Vaishali T. Thakkar. Development of Sustained Release Pellets of Galantamine HBr by Extrusion Spheronization Technique Incorporating Risk based QbD Approach. Research J. Pharm. and Tech 2018; 11(11): 4899-910.doi.org/ 10.5958/0974-360X.2018.00892.2

 

 

Accepted on 20.05.2021          © RJPT All right reserved

Research J. Pharm. and Tech 2021; 14(10):5319-5324.