The synergistic effect of Landolphia owariensis latex and Eudragit® L-100-coated capsules on the in vitro controlled release of metronidazole for possible colon targeting

Nicholas C Obitte, Amarauche Chukwu


The overall objective of this present investigation was to determine the synergistic potentiality of Landolphia owariensis latex (LOL) and Eudragit® L-100 as hydrophobic polymeric agents in ensuring controlled drug release for possible
colon-targeted delivery of metronidazole. Metronidazole granules were prepared by the wet granulation method and manually encapsulated. The entire capsule surface was first coated with Eudragit® L-100 (primary coating). Secondly half
(50%) or five-sixth (5/6 or 83%) of the capsule surface was coated atop the primary coating with LOL (secondary coating). Two different granule size fractions were isolated and compared. Parallel gradient in vitro drug release studies were carried out in media of pH 1.2, 6.8 and 7.4, respectively. The dissolution data were subjected to kinetic treatment. Results showed that the least quantity of drug release took place at pH 1.2 followed by pH 6.8, with greatest drug release taking place at pH 7.4. Capsule surface coated with LOL significantly (P<0.05) affected drug release and time of release. Matrix former(binder) concentration had no significant (P<0.05) effect on drug release, but particle size did. More than one drug release mechanisms were operational and most capsules with 50% surface coated with LOL recorded higher Dissolution efficiency (DE) but lower Mean dissolution time (MDT) than those of 83%. In conclusion, the use of Eudragit® L-100 and LOL as primary and secondary capsule coatings respectively have demonstrated competence in controlling drug release and thus
may hold promise at preferentially targeting metronidazole to the colon against amebic diseases.

Full Text:



Toshikiro K, Kazutaka H. Gastrointestinal transit and drug absorption.

Biol Pharm Bull 2002;25:149-64.

Kshirsagar NA. Drug delivery systems. Indian J Pharmacol 2000;32:S54-61.

Gupta VK, Beckert TE, Price JC. A novel pH- and time-based multi-unit

potential colonic drug delivery system, I: Development. Int J Pharm


Chaurasia M, Chourasia MK, Jain NK, Jain A, Soni V, Gupta Y, et al.

Cross-linked guar gum microspheres: A viable approach for improved

delivery of anticancer drugs for the treatment of colorectal cancer.

AAPS PharmSciTech 2006;7:74.

Walsh JA. Problems in recognition and diagnosis of amoebiasis:

Estimation of the global magnitude of morbidity and mortality. Rev

Infect Dis 1986;8:228-38.

World Health Organization. Amoebiasis. WHO Wkly Epidemiol Record


Nasra MA, EL-Massik MA, Naggar VF. Development of metronidazole

colon-specific delivery systems. Asian J Pharm Sci 2007;2:18-28.

Martindale. “The Complete Drug Reference”. 34th Ed., ed. by Sean C.S.,

The Pharmaceutical Press; 2005.

van den Mooter G, Kinget R. Oral colon-specific drug delivery: A review.

Drug Del 1995;2:81-93.

Rama Prasad YV, Krishnaiah YS, Satyanarayana S. Trends in colonic drug delivery: A review. Indian Drugs 1996;33:1-10.

Obitte NC, Chukwu A, Onyishi VI, Obitte BC. The Physicochemical

evaluation and applicability of Landolphia owariensis latex as a release

modulating agent in its admixture with Carbosil® in Ibuprofen-loaded

self-emulsifying oil formulations. Int J Appl Res Prod 2009;2:27-43.

Obitte NC, Chukwu A, Onyishi VI. The use of a pH-dependent and

non pH-dependent natural hydrophobic biopolymer (Landolphia

owariensis latex) as capsule coating agents in in vitro controlled release

of metronidazole for possible colon targeted delivery. Int J Appl Res

Prod 2010;2:1-17.

Adikwu MU, Ossai AO. Evaluation of Landolphia dulcis pseudolatex as a

granulating fluid for aminophylline tablets. Acta Pharma 1994;44:157-62.

Obitte NC, Chukwu A. Physicotechnical properties of theophylline

capsules prepared with Tacca involucrata starch. West J Pharm


Akhgari A, Garekani HA, Sadeghi F, Azimaie M. Statistical optimization

of indomethacin pellets coated with pH dependent methacrylic

polymers for possible colonic drug delivery. Int J Pharm 2005;305:22-30.

Kuksal A, Ashok KT, Narendra KJ, Subheet J. Formulation and in vitro,

in vivo evaluation of extended- release matrix tablet of Zidovudine:

Influence of combination of hydrophilic and hydrophobic matrix

Formers. AAPS PharmSciTech 2006;7:E1-9.

Ibekwe VC, Kendall RA and Basit AW. Drug delivery to the colon, The

Drug Delivery Companies Report, Spring/Summer, Pharmaventures

Ltd; 2004.

Evans DF, Pye G, Bramley R, Clark AG, Dyson TJ, Hardcastle JD.

Measurement of gastrointestinal pH profiles in normal ambulant human

subjects. Gut 1988;29:1035-41.

Costa P, Lobo JM. Modeling and comparison of dissolution profiles. Eur

J Pharm Sci 2001;13:123-33.

Sreenivas SA, Hiremath SP, Godbole AM. Ofloxacin ocular inserts:

Design, formulation and evaluation. Int J Pharm Therap 2006;5:159-62.

Korsemeyer RW, Gurny R, Doelker EM, Buri P, Peppas NA. Mechanism

of solute release from porous hydrophilic polymers. Int J Pharm


Dubey S, Bajpai SK. Poly (methacrylamide-co-acrylicacid) hydrogels for gastrointestinal delivery of theophylline. I. Swelling characterization.

J Appl Pol Sc 2006;101:2995-3008.

Hixson AW, Crowell JH. Dependence of reaction velocity upon surface and agitation 1: Theoretical consideration. Ind Eng Chem 1931;23:923-31.

Pather I, Russell I, Syce JA, Neau SH. Sustained release theophyline

tablets by direct compression, Part 1: Formulation and in vitro testing.

Int J Pharm 1998;164:1-10.

Emami J. In vitro - in vivo correlation: From theory to applications J

Pharm Pharmaceut Sci 2006;9:169-89.

Steed KP, Clive GW, Washington N. Drug delivery to the large intestine.

Physiological Pharmaceutics. England: Ellis Horwood Ltd; 1989. p.


McCoy JJ, Mann BJ, Petri WA. Adherence and cytotoxicity of Entamoeba

histolytica or how lectins let parasites stick around. Infect Immun


Stilwell GG. Amebiasis: Its early history. Gastroenterology 1955;28:606-22.

Petri WA, Clark G, Diamond LS. Host-parasite relationships in amebiasis.

J Infect Dis 1994;169:483-84.

Ali N, Davoud H, Farnaz M, Nita T. Effect of various surfactants and

their concentration on controlled release of captopril from polymeric

matrices. Acta Pharm 2008;58:151-62.

Bomba M, Puisieux F, Marty JP Carstensen JT. Release mechanisms in

gel forming sustained release preparations. Int J Pharm 1979;2:307-15.

Obitte NC, Chukwu A. Dissolution characteristics of theophylline

capsules containing Tacca involucrata starch as binder. West Afr J Pharm


Ashford M, Fell J, Attwood D, Sharma H, Woodhead P. In vitro

investigation into the suitability of pH dependent polymer for colonic

targeting: An in-vivo investigation into the suitability of pH dependent

polymers for colonic targeting. Int J Pharm 1993;95:193-9.

Leopold CS, Eikeler D. Basic coating polymers for the colon-specific

drug delivery in inflammatory bowel disease. Drug Dev Ind Pharm


Kumar P, Singh S, Mishra B. Colon targeted delivery systems of

metronidazole based on osmotic technology: Development and

evaluation. Chem Pharm Bull 2008;56,9:1234-42.

Abdou HM. Dissolution. Remington: The science and practice of

pharmacy. 20th ed. vol.1. In: Limmer D, editor. Philadelphia, USA:

Lippincott Williams and Wilkins; 2000.

Arshia S, Manna PK, Paranjothy KL, Manjula M. Entrapment of

andrographolide in cross-linked alginate pellets: I, formulation and

evaluation of associated release kinetics. Pak J Pharm Sci 2007;20:1-9.

Peppas NA. Analysis of Fickian and non-Fickian drug release from

polymers. Pharm Acta Helv 1985;60:110-1.

Lourdes O, Manuela I, Rosa M, Hernández AR, Gascón JL. Preparation

of sustained release hydrophilic matrices by melt granulation in a

high-shear mixer. J Pharm Pharmaceut Sci 2005;8:132-40.

Thombre AG, Cardinal JR, DeNoto AR, Herbig SM, Smith KL. Asymmetric

membrane capsule for osmotic drug delivery, I: Development of

manufacturing process. J Control Rel 1999;57:55-64.

Herbig SM, Cardinal JR, Korsmeyer RW, Smith KL. Asymmetric

membrane tablet coatings for osmotic drug delivery. J Control Rel


Pratim KC, Mahendra SR, Mousumi KP, Chetan SC. Asymmetric

membrane capsule for osmotic delivery of flurbiprofen. Acta Pharm




  • There are currently no refbacks.