Ghosh T., Karki V. S., Ghosh A., Kumar A., Hullatti P.


Objective: The objective of the work was to formulate coated microbeads using core-coat technique for chronotherapeutic delivery of Carvedilol (cd).

Methods: Sodium alginate microbeads containing cd was formulated by ionic gelation method using calcium chloride as gelling agent. Microbeads were then coated with acrylcoat L 100 (acL 100), acrylcoat S 100 (acS 100), ethyl cellulose (EC), and acrylcoat E30 D (acE 30D) in different ratio. Formulated batches were evaluated using FTIR, particle size measurement, percent entrapment efficiency, micrometric properties, swelling studies, loose surface crystal studies, percentage moisture loss. The formulations were then subjected to in-vitro dissolution studies. Cumulative release data was then subjected to different dissolution models reported in literature.

Results:  Formulated batches of microbeads were within acceptable particle size range with good to fair flow properties. Entrapment efficiency was in the range of 64% to 99.52%. Loose surface crystal study revealed successful drug entrapment within a range of 2.11 to 9.93%. Swelling studies revealed maximum swelling in alkaline phosphate buffer pH 7.4 solution and percentage moisture loss was within 0.24% to 7.55%. SEM showed microbeads to be spherical in nature and FTIR study exhibited compatibility among the drug and polymer. In vitro release study was carried out for first 3 hours in 0.1N HCl and subsequently for 7 hours in phosphate buffer solution pH 7.4. Formulation code AC3, AC4, LA4 and LA6 were found in line with our objective of chronotherapeutic drug delivery.

Conclusion: Sodium alginate beads loaded with cd and coated with different ratios of coating solutions were successfully formulated and evaluated to optimize the best possible combinations of coat-core ratio for chronotherapeutic delivery


Chronotherapeutic dug delivery, Carvedilol, Core-coat technique, Microbeads


Bellamy N, Sothern RB, Campbell J. Rhythmic variations in pain perception in osteoarthritis of the knee. J Rheumatol 1990;17:364-72.

Ghosh T, Ghosh A, Kumar A. Chronotherapeutic Drug Delivery: A Way Forward to Treat Rhythm Guided Diseases. J Pharm Sci & Res 2017;9:1894- 8.

De Geest BG, Mehuys E, Laekeman G, Demeester J, De Smedt SC. Pulsed drug delivery. Expert Opin Drug Deliv 2006;3:459-62.

Youan BB. Chronopharmaceutics: gimmick or clinically relevant approach to drug delivery? J Control Release 2004;98:337–53.

Shidhaye SS, Lotlikar VM, Ghule AM, Phutane PK, Kadam VJ. Pulsatile delivery systems: An approach for chronotherapeutic diseases. Sys Rev Pharm 2010;1:55–61.

Pasic J, Shapiro D, Motivala S, Hui KK. Blood pressure morning surge and hostility. Am J Hypertens 1998;11:245–50.

Ura, J. Shirachi D. Ferrill M. The chronotherapeutic approach to pharmaceutical treatment. California Pharmacist 1992;23:46-53.

Smolensky, M.H. Labreque G. Chronotherapeutic. Pharm News1997;2:10-6.

Dhalleine C, Assifaoui A, Moulari B, Pellequer Y, Cayot P, Lamprecht A, Chambin O. Zinc-pectinate beads as an invivo self-assembling system for pulsatile drug delivery. Int J Pharm 2011; 414:28-34.

Kunjachan S, Jose S. Understanding the mechanism of ionic gelation for synthesis of chitosan nanoparticles using qualitative techniques. Asian J Pharmaceutics 2010;4: 148-3.

Mattam J, Sailaja K. Preparation and evaluation of sulfasalazine loaded sodium alginate microbeads for sustained delivery. Asian J Pharma & Clin Res 2016; 9:72-6.

Andrea C, Giulia A, Pasquale DG, Francesca S, Rita PA, Paola R. Novel core-shell chronotherapeutic system for the oral administration of ketoprofen. J of Drug Del Sci & Tech 2016;32:126-31.

Mazumder R, Nath LK, Haque A, Maity T, Choudhury PK, Shrestha B et.al. Formulation and in vitro evaluation of natural polymers based Microspheres for colonic drug delivery. IJPPS 2010;2:211-9.

Girhepunje KM, Piillai K, Pal RS, Gevariya HB, Thirumoorthy N. Celecoxib loaded microbeads: a targeted drug delivery for colorectal cancer. Int J of Current Pharma Res 2010;2:46-55.

Saparia B, Murthy RSR and Solanki, Preparation and evaluation of chlorquine phosphate microspheres using cross linked gelatin for long term drug delivery. Indian J Pharm Sci 2002;64:48-52.

Sangeetha S, Sakthisaravanan V, Komala M, Harish G, Sivakumar V. Design and evaluation of gastro retentive beads of theophylline by Ionotropic gelation. IJPPS 2010;2:99-101.

Ghosh A, Biswas S, Ghosh T. Preparation and evaluation of silymarin β-cyclodextrin Molecular inclusion complexes. J of young pharmacists 2011;3:205-10

GN Vishal, Gowda D, Balamuralidhara V, Khan SM. Formulation and evaluation of olanzapine matrix pellets for controlled release. Daru 2011;19:249-56.

Lachman L, Lieberman HA. Joseph LK, editors. The theory and practice of industrial pharmacy, 3rd Edition, Philadelphia: Lea & Febiger;1986.

Ghosh A, Saha A, Das S, Ghosh T. Formulation and in-vitro evaluation of zidovudine loaded ECmicrocapsules. IJPSR 2011;2: 289-97

Varshosaz J, Jaffarian A, Golafshan S, Colon-specific delivery of mesalazine chitosan microspheres. J of Microencapsulation 2006;23:329- 39.

Dandagi PM, Mastihomath VS, Patil MB, Manvi FV, Gadad AP, Sharma R. Development and evaluation of theophyllin and salbutamol sulphate sustained release matrix tablets. Indian J Pharm Sci 2005;67:598-02.

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