Formulation and Evaluation of Gastroretentive Floating
Microspheres of Labetalol Hydrochloride
Nadeem
Shaikh1*; Sagar Patidar2; Manish Mukati2; Rakesh
Punasiya2
1.Ali-Allana College of Pharmacy Akkalkuwa, Dist. Nandurbar
Maharashtra India 425415
2. Yogeshwar College of pharmacy Piplaj, Dist. Barwani Madhya
Pradesh India 451551
*Correspondence: nadeemshaikh3090@gmail.com;
DOI: https://doi.org/10.71431/IJRPAS.2026.5104
|
Article
Information
|
|
Abstract
|
|
Research Article
Received: 13/01/2026
Accepted: 26/01/2026
Published:31/01/2026
Keywords
Labetalol hydrochloride,
Gastroretentive drug delivery, Floating microspheres, Sustained release,
Ethyl cellulose, Eudragit RS100.
|
|
Labetalol hydrochloride is an
antihypertensive drug exhibiting extensive first-pass metabolism and a
relatively short biological half-life, necessitating frequent dosing which
may reduce patient compliance. The present investigation aimed to formulate
and evaluate gastroretentive floating microspheres of labetalol hydrochloride
to prolong gastric residence time and provide sustained drug release.
Floating microspheres were prepared by the emulsion solvent diffusion method
using ethyl cellulose and Eudragit RS100 as release-controlling polymers and
polyvinyl alcohol as a surfactant. Preformulation studies confirmed the
physicochemical suitability of the drug. FT-IR studies revealed no chemical
interaction between the drug and polymers. The prepared microspheres were
evaluated for flow properties, particle size, percentage yield, entrapment
efficiency, in vitro buoyancy, and in vitro drug release. The microspheres
exhibited good flow properties, high buoyancy (76–94%), and sustained drug
release up to 12 hours. Among all formulations, F8 showed optimum
characteristics with highest entrapment efficiency (97.2%), buoyancy (94%),
and controlled drug release up to 12 hours. The study concludes that
gastroretentive floating microspheres of labetalol hydrochloride can be an
effective approach to enhance oral bioavailability and improve patient
compliance.
|
INTRODUCTION
Oral drug delivery is the most convenient and
widely accepted route due to ease of administration and better patient
compliance. However, drugs with short half-life, narrow absorption window, or
extensive first-pass metabolism often show reduced bioavailability. Gastroretentive
drug delivery systems (GRDDS) are designed to retain the dosage form in the
stomach for a prolonged period, thereby enhancing drug absorption and
therapeutic efficacy.
Floating microspheres are low-density
multiarticulate systems that remain buoyant over gastric contents, enabling
prolonged gastric retention and controlled drug release. Labetalol
hydrochloride, a combined alpha- and beta-adrenergic blocker, is widely used in
the management of hypertension but requires frequent dosing due to its short
half-life. Hence, it was selected as a suitable candidate for the development
of a gastroretentive floating microsphere system.
MATERIALS AND METHODS
Floating microspheres of labetalol
hydrochloride were prepared by the emulsion solvent diffusion method using
ethyl cellulose and Eudragit RS100 as polymers. Polyvinyl alcohol was used as a
surfactant. The prepared microspheres were subjected to Preformulation and
evaluation studies including flow properties, particle size analysis,
percentage yield, entrapment efficiency, in vitro buoyancy, and in vitro drug
release studies.
Table 1. List of materials used
|
Sr. No.
|
Name of the Material
|
Manufacturer /Supplier
|
Role in formulation
|
|
1.
|
Labetalol hydrochloride
|
Gift sample from Glan
Pharma Pvt.
Ltd., Hyderabad.
|
Active ingredient
|
|
2.
|
Ethyl cellulose
|
Loba Chemie
Pvt. Ltd.Mumbai
|
Polymer
|
|
3.
|
Eudragit RS100
|
Yarrow Chem
Mumbai
|
Polymer
|
|
4.
|
Polyvinyl Alcohol
|
Loba Chemie
Pvt. Ltd.Mumbai
|
Stabilizing agent
|
|
5.
|
Ethanol
|
Loba Chemie
Pvt. Ltd.Mumbai
|
Solvent
|
|
6
|
Dichloromethane
|
Loba Chemie
Pvt. Ltd.Mumbai
|
Solvent
|
|
7
|
Hydrochloric acid
|
Loba Chemie
Pvt. Ltd.Mumbai
|
Solvent
|
|
|
|
|
|
Table 2. List of Equipment /Instruments used
|
Sr. No.
|
Equipment’s
|
Manufacturers/Suppliers
|
|
1.
|
Electronic Weighing Balance
|
MC Dalal.
|
|
2.
|
FT-IR
|
Nicolet, Germany.
|
|
3.
|
Uv-visible Spectrophotometer
|
Shimadzu 1800
|
|
4.
|
Magnetic Stirrer
|
Remi instruments, Mumbai.
|
|
5.
|
Scanning Electron Microscope
|
Hitachi, Japan.
|
|
6.
|
Optical Microscope
|
Sigma Scientific Instrumentation.
|
|
7.
|
pH meter
|
Electronics India
|
|
8.
|
Hot air oven
|
Lab Tech
|
|
9.
|
Dissolution Apparatus
|
EI Instruments
|
|
10.
|
Stability chamber
|
Remi Che-6
Plus
|
Table 3. Composition of Formulation
|
F. CODE
|
Labetalol Hydrochloride
(mg)
|
Ethyl Cellulose
(mg)
|
Eudragit
RS100
(mg)
|
Polyvinyl Alcohol
(0.5%w/v)
(ml)
|
Ethanol:
Dichloromethane
(1:1)
|
|
F1
|
100
|
100
|
--
|
100
|
10:10
|
|
F2
|
100
|
200
|
--
|
100
|
10:10
|
|
F3
|
100
|
300
|
--
|
100
|
10:10
|
|
F4
|
100
|
--
|
100
|
100
|
10:10
|
|
F5
|
100
|
--
|
200
|
100
|
10:10
|
|
F6
|
100
|
--
|
300
|
100
|
10:10
|
|
F7
|
100
|
100
|
100
|
100
|
10:10
|
|
F8
|
100
|
200
|
100
|
100
|
10:10
|
|
F9
|
100
|
100
|
200
|
100
|
10:10
|
RESULT
AND DISCUSSION
Preformulation
studies indicated that labetalol hydrochloride possessed suitable
physicochemical characteristics for formulation. The λmax was found at 246 nm
and the drug obeyed Beer-Lambert’s law in the concentration range of 20–100
µg/ml (R² = 0.999). FT-IR spectra confirmed the absence of any drug–polymer
interaction.
λmax Determination by UV Spectroscopy:
The maximum absorption (λmax) of Labetalol HCl Was found at 246.00 nm and iso-absorptive point at 243.48 nm. Absorption for a series of standard
Solutions were recorded at selected wavelength.
Fig: - 01 Absorption spectra
of labetalol HCL
CHEMICAL COMPATIBILITY:
FT-IR Spectroscopic Studies:
FT-IR spectroscopy gives the possible information about the
interaction between the drug and the polymer. The compatibility between drug
and polymer was confirmed by using FT-IR spectroscopy. Infrared spectroscopic
analysis for drug (Labetalol hydrochloride), drug polymer admixture and
formulations were carried out.
Fig: -02 FT-IR spectrum of Labetalol Hydrochloride
Preformulation studies of labetalol hydrochloride microspheres
All
formulations were evaluated
for flow properties and the results were shown in table
Table:04 Flow property measurements of Microspheres
|
F. code
|
Bulk density (g/ml) *
|
Tapped density (g/ml) *
|
Carr’s Index (%)
*
|
Hausner’sratio
|
Angle of repose (θ)
|
|
F1
|
0.32± 0.009
|
0.35± 0.009
|
6.37
± 1.72
|
1.01
|
36°52
|
|
F2
|
0.34± 0.012
|
0.36±0.007
|
6.51 ± 1.91
|
1.06
|
37°68
|
|
F3
|
0.47
±0.03
|
0.52
± 0.02
|
10.63
± 0.03
|
1.11
|
25°41
|
|
F4
|
0.34 ± 0.016
|
0.36 ± 0.011
|
6.55 ± 1.90
|
1.05
|
35°18
|
|
F5
|
0.35
± 0.009
|
0.38±0.009
|
6.69
± 2.05
|
1.07
|
39°47
|
|
F6
|
0.35± 0.011
|
0.38± 0.006
|
6.73 ± 1.84
|
1.07
|
34°55
|
|
F7
|
0.32±0.05
|
0.39±0.06
|
6.78
± 0.09
|
1.04
|
38°52
|
|
F8
|
0.49 ±0.01
|
0.54 ± 0.01
|
10.20 ± 0.02
|
1.10
|
33°50
|
|
F9
|
0.31±0.04
|
0.37±0.08
|
7.10±0.07
|
1.04
|
36°40
|
Inference: The formulations F3 and F8 showed good flow property.
All
formulations exhibited acceptable flow properties. Particle size ranged from
55.4 µm to 219.33 µm and increased with polymer concentration. Percentage yield
ranged between 48.33% and 86.25%, while entrapment efficiency varied from 80.5%
to 97.2%. In vitro buoyancy studies demonstrated that microspheres remained
buoyant for more than 12 hours. In vitro drug release studies revealed
sustained release behavior, with formulation F8 showing controlled drug release
up to 12 hours and was selected as the optimized formulation.
Table:05 In vitro drug release for all formulations
|
Time
(hrs.)
|
|
PERCENTAGE
|
DRUG
|
RELEASE
|
|
|
|
|
|
|
|
Time
(hrs.)
|
|
F1
|
F2
|
F3
|
F4
|
F5
|
F6
|
F7
|
F8
|
F9
|
|
|
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
0
|
|
2.55
|
2.25
|
1.8
|
2.16
|
0.7
|
1.51
|
0.36
|
1.62
|
1.98
|
|
0.5
|
|
15.54
|
9.38
|
9.38
|
6.5
|
10.71
|
3.88
|
1.44
|
10.54
|
9.02
|
|
1
|
|
29.48
|
16.68
|
16.68
|
20.16
|
16.86
|
10.76
|
23.49
|
13.27
|
10.38
|
|
1.5
|
|
38.38
|
32.08
|
21.18
|
28.8
|
25.24
|
16.55
|
34.28
|
22.6
|
20.93
|
|
2
|
|
47.59
|
36.84
|
34.83
|
45.63
|
35.6
|
27.9
|
37.27
|
24.01
|
24.76
|
|
3
|
|
59.21
|
45.79
|
42.05
|
49.28
|
53.35
|
40.35
|
51
|
35.35
|
46.09
|
|
4
|
|
61.59
|
52.77
|
56.45
|
70.33
|
61.05
|
47.81
|
60.92
|
37.44
|
59.38
|
|
5
|
|
91.54
|
66.75
|
64.8
|
75.87
|
71.61
|
70.29
|
72.1
|
47.83
|
68.7
|
|
6
|
|
94.38
|
73.77
|
69.37
|
86.78
|
75.08
|
83.83
|
80.98
|
50.06
|
80.62
|
|
7
|
|
96.9
|
84.64
|
81.44
|
96.86
|
81.19
|
-
|
94.44
|
57.43
|
86.16
|
|
8
|
|
-
|
87.52
|
85.55
|
-
|
85.65
|
-
|
-
|
62.81
|
90.86
|
|
9
|
|
-
|
97.8
|
87.89
|
-
|
90.42
|
-
|
-
|
73.73
|
93.8
|
|
10
|
|
-
|
-
|
93.21
|
-
|
-
|
-
|
-
|
87.83
|
96.94
|
|
11
|
|
-
|
-
|
99.04
|
-
|
-
|
-
|
-
|
100.2
|
98.25
|
|
12
|
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Fig: -03 In vitro release of Optimized
formulations
The comparative in vitro release profile for Labetalol Hydrochloride Microspheres (F3&F8) were shown in Figure No. 29.
The results of formulations show (99.04% and 100.2%) controlled release
up to 12th The entrapment efficiency was found to be higher
in F3- 93.4%±0.21 and F8- 97.2% comparatively with other formulations.
Therefore, F3 and F8 were selected as
formulations
CONCLUSION
Gastroretentive floating microspheres of labetalol
hydrochloride were successfully formulated using ethyl cellulose and Eudragit
RS100. The optimized formulation (F8) demonstrated excellent buoyancy, high
entrapment efficiency, and sustained drug release up to 12 hours. This delivery
system has the potential to improve oral bioavailability, reduce dosing
frequency, and enhance patient compliance in the management of hypertension.
REFERENCES
1.
Ramu S,
Suneetha D, Srinivas R & Ramakrishna G. Formulation and
Evaluation of Gastroretentive Clarithromycin Floating Tablets, International
Journal Of pharmaceutical, Chemical and Biological Sciences,2015; 5(4): 883-895.
2.
Pant Shailaja, Badola Ashutosh, kothiyal
Preeti “A REVIEW ON GASTRORETENTIVE DRUG DELIVERY SYSTEM” International Journal
of Research and Development in
Pharmacy and Life Sciences, June – July, 2016;5(4):2178-2179.
3.
Shaikh
Siraj, Molvi Khurshid. I,
Sayyed Nazim
“Various Perspectives of Gastro retentive Drug Delivery System:
A Review” American
Journal of Advanced
Drug Delivery,2013;1(4):1-2.
4.
Shakya.R
, Thapa P & Saha.NR. In Vitro and In Vivo Evaluation of Gastroretentive Floating Drug Delivery
System of Ofloxacin, Asian Journal of Pharmaceutical Sciences,2013; 1(1):
91-98.
5.
Ali J,
Arora S, Ahuja A, Babbar AK, Sharma RK, Khar RK, Baboota S. Formulation
and Development of Hydrodynamically balanced system for
metformin: in vitro and in vivo Evaluation. European journal
of Pharmaceutics and biopharmaceutics.2007 Aug 31;67(1):196-201.
6.
Katakam
V.K, Somagoni J.M, Reddy S, Eaga C.M, Rallabandi B.R.C and Yamsani MR. Floating
Drug Delivery Systems: A Review. 2010;4(2):610-647.
7. Vinod K.R, Vasa S, Anbuazaghan S, Banji D, Padmasri A and Sandhya S.
Approaches For gastrotentive drug delivery systems. IJABPT. 2010;1(1) 589-60.
8.
Dhole AR, Gaikwad PD, Bankar VH, Pawar SP.
A Review on Floating Multiparticulate Drug Delivery System- A Novel Approach to
Gastric Retentionists. 2011; 6(2):
205 -211.
9.
Garg R and Gupta G.D. Progress in controlled Gastroretentive delivery. Trop J PharRes.
2008; 7(3):1055-1066.
10. Ganesh N.S, Suraj Mahadev Ambale, Ramesh B, Kiran B and Deshpande. An Overview On limitations of Gastroretentive drug delivery System. IJPSRR.2011; 8 (2):133-139.
11.
Kawatra M, Jain U, Ramana J. Recent
Advances in Floating Microspheres as Gastro-Retentive drug delivery System: A
Review. International Journal of Recent Advances in Pharmaceutical Research. July 2012; 2(3): 5-23.
12. Dhadde
Gurunath S., Mali Hanmant
S., Raut Indrayani D., Nitalikar Manoj M., Bhutkar Mangesh
A., A Review on Microspheres: Types, Method of Preparation,
Characterization and Application,Asian Journal of Pharmacy
and Technology, June 2021;11(2):1-2.
13.
Tarun Virmani,
et. Al., Pharmaceutical Application of Microspheres: An Approach
for The Treatment of Various Diseases, International Journal of Pharmaceutical
Sciences and Research, 2017, 7 Page
3252-3260.
14.
B. Sree Giri Prasad, et. Al., Microspheres
as Drug Delivery System – A Review,
Journal Of Global Trends
in Pharmaceutical Sciences, (2014), 5(3), Page 1961–1972.
15.
Saravana
Kumar K, et. Al., A Review on Microsphere for Novel Drug delivery System, Journal of Pharmacy Research, 2012,5(1),
Page 420-424.
16.
Pande AV,
Vaidya PD, Arora M, Dhoka MV. In Vitro and In Vivo Evaluation of
Ethyl Cellulose Based Floating Microspheres of Cefpodoxime Proxetil. International Journal of Pharmaceutical and Biomedical Research. 2010, 1(4):122-128.
17.
Mastiholimath.V. S, Dandagi PM, Gadad AP,
Mathews R, Kulkarni A. R. In vitro And in vivo evaluation of Ranitidine hydrochloride ethyl cellulose floating Microparticles. J. Microencapsulation. 2008, 25(5), 307-314.
18.
Ghodake JD, Vidhate JS, Shinde DA, Kadam AN. Formulation and Evaluation of Floating
Microsphere Containing Anti-Diabetic (Metformin Hydrochloride) Drug.
International Journal of PharmTech
Research. 2010, 2(1): 378-384
19.
Kamila MM, Mondal N, Ghosh LK, Gupta BK.
Multiunit floating drug delivery System of rosiglitazone maleate: development,
characterization, statistical Optimization of drug release and in vivo
evaluation. AAPS PharmSciTech. 2009, 10(3):887-99
20.
Gattani YS, Kawtikwar PS, Sakarkar DM.
Formulation and evaluation of Gastro Retentive Multiarticulate Drug delivery
system of Aceclofenac International Journal
of Chemtech Research. 2009, 1(1): 1-10.
21.
Fentie M, Belete A, Mariam TG Formulation
of Sustained Release Floating Microspheres of
Furosemide from Ethyl cellulose and Hydroxypropyl Methylcellulose
Polymer Blends. J Nano
med Nanotechnology. 2015, 6: 262.
22. Peru
Mandla PK, Priya S. Formulation And In Vitro Evaluation of Floating
Microspheres of Dextromethorphan Hydrobromide. International Journal
of Pharmacy and Pharmaceutical Sciences. 2014, 6 (4): 206-210.
23.
Panwar MS, Tanwar YS. Development and
characterization of sustain release Gastro retentive floating microsphere of
diltiazem hydrochloride for the treatment of hypertension. Asian J Pharm 2015; 9: 107-12.
24.
Pandey N, Sah AN, Mahara K. Formulation
and Evaluation of Floating Microspheres of Nateglinide. International Journal of Pharma Sciences and Research.
2016, 7 (11): 453-464.
25.
Kaushik AY, Tiwari AK, Gaur A. Preparation
of Floating Microspheres of Valsartan:
In-Vitro Characterization. Int. J. Res. Ayurveda Pharm. 2015; 6(1):124-130.
26.
Saxena A, Gaur K, Singh V, Singh RK, Dashora A. Floating Microspheres as Drug Delivery System. AJPPS 2014, 1(2):27-36.
27. Devi NA, Vijendar C, Anil Goud K,
Anil Kumar D, Khaja M and Anil A.
Preparation and Evaluation
of Floating Microspheres of Cefdinir in Treatment of Otitis
Media and Respiratory Tract Infections. J Pharmacovigilance 2016, 4:3
28. Bhuvaneswari
S, Manivannan S, Akshay M, Nify F. Formulation and Evaluation of Gastroretentive Microballoons of Acebrophylline for the Treatment
of Bronchial Asthma. Asian J Pharm Clin Res, 2016, 9(5):105-111.
29.
Verma NK, Alam G, Mishra JN, Vishwakarma DK. Formulation
and Characterization of floating
microspheres of Ibuprofen. Int J Res Pharm Sci 2015, 5(1); 18 – 22.31.
30.
Sharma MK. Formulation and
Characterization of Floating Microspheres of
Acarbose by Solvent Evaporation Method. Mintage journal of
Pharmaceutical & Medical Sciences. 2016, 5 (3): 3-7.
31.
Chouhan M, Chundawat AVS, Chauhan C. S.
Development and Characterization of Floating Microspheres of Esomeprazole
Magnesium Trihydrate by Solvent Evaporation Method. IJPSR, 2017; Vol. 8(2): 686-697
32.
Yadav S, Nyola NK, Jeyabalan
G, Gupta M. Gastroretentive drug delivery System:
a concise review.
Int J Res Pharm Sci 2016, 6(2); 19 –24.
33.
Hafeez A, Maurya A, Singh J, Mittal A,
Rana L. An overview on floating Microsphere: Gastro Retention Floating drug delivery system
(FDDS). The Journal of Phytopharmacology 2013;
2(3): 1-12.
34.
Patel S, Aundhia C, Seth A, Shah N, Gohil
D, Ramani V. Design, Development, Evaluation and Optimization of Micro balloons
of Telmisartan. Saudi J. Med. Pharm. Sci., Vol-4, Iss-1A (Jan, 2018): 70-89
35.
Shivani BR, Sailaja AK. Preparation and
Evaluation of Floating Microspheres of Omeprazole Microspheres by Solvent
Evaporation Method. International Journal Of
Basic and Applied Chemical Sciences.2015, 5 (3):67-78.
36.
J Josephine LJ, Mehul RT, Wilson B, Shanaz B, Bincy
R. Formulation and In Vitro Evaluation of Floating Microspheres
of Anti-Retro Viral Drug as a Gastro Retentive Dosage Form. IJRPC. 2011, 1(3):
519-527.
37.
Vasava K, Rajesh KS, Jha LL. Formulation
and Evaluation of Floating Microspheres of Cephalexin. International Journal of Pharmaceutical Sciences Review and Research. 2011, 11(2): 69-75.
38.
Sharma AK, Keservani RK., Dadar Wal SC,
Choudhary YL, Ramteke S. Formulation and in vitro characterization of
cefpodoxime proxetil gastroretentive Micro balloons DARU. 2011,19(1): 33-40.