Rapidly disintegrating tablets of metoclopramide hydrochloride using novel chemically modified cellulose

Aloorkar Nh

Description

ABSTRACT
The purpose of the study was to modify cellulose using hydrochloride salt of 2-aminoethanoyl chloride with optimum hydrophilic and hydrophobic properties to impart it a superdisintegrant activity and also to formulate and evaluate rapidly disintegrating tablets of metoclopramide hydrochloride using this novel chemically modified cellulose. A novel polymer, chemically modified cellulose was synthesized by chemically modifying microcrystalline cellulose with hydrochloride salt of 2-aminoethanoyl chloride. The formation of novel polymer was confirmed by Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy and by differential scanning calorimetric (DSC) and elemental analysis. The toxicity study proved the novel modified cellulose to be non toxic. Rapidly disintegrating tablets of metoclopramide hydrochloride were prepared using novel modified cellulose and compared for the release of drug with control formulation, prepared using non modified microcrystalline cellulose. The tests like wetting time, water absorption ratio and in vitro disintegration time were carried out to elucidate the relationship between them. The study revealed that novel modified cellulose in a concentration of 2% released the drug faster than at a concentration higher than that. Hence it could be concluded that microcrystalline cellulose, a polymer which is devoid of superdisintegrant activity, can suitably be modified by controlled chemical modification of it with hydrochloride salt of 2-aminoethanoyl chloride or similar groups with optimum hydrophilicity and hydrophobicity to convert it into a superdisintegrant material. It can also be concluded that rapidly disintegrating tablets of metoclopramide hydrochloride can suitably be developed for the efficient management of emesis.
RESUMEN
The purpose of the study was to modify cellulose using hydrochloride salt of 2-aminoethanoyl chloride with optimum hydrophilic and hydrophobic properties to impart it a superdisintegrant activity and also to formulate and evaluate rapidly disintegrating tablets of metoclopramide hydrochloride using this novel chemically modified cellulose. A novel polymer, chemically modified cellulose was synthesized by chemically modifying microcrystalline cellulose with hydrochloride salt of 2-aminoethanoyl chloride. The formation of novel polymer was confirmed by Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy and by differential scanning calorimetric (DSC) and elemental analysis. The toxicity study proved the novel modified cellulose to be non toxic. Rapidly disintegrating tablets of metoclopramide hydrochloride were prepared using novel modified cellulose and compared for the release of drug with control formulation, prepared using non modified microcrystalline cellulose. The tests like wetting time, water absorption ratio and in vitro disintegration time were carried out to elucidate the relationship between them. The study revealed that novel modified cellulose in a concentration of 2% released the drug faster than at a concentration higher than that. Hence it could be concluded that microcrystalline cellulose, a polymer which is devoid of superdisintegrant activity, can suitably be modified by controlled chemical modification of it with hydrochloride salt of 2-aminoethanoyl chloride or similar groups with optimum hydrophilicity and hydrophobicity to convert it into a superdisintegrant material. It can also be concluded that rapidly disintegrating tablets of metoclopramide hydrochloride can suitably be developed for the efficient management of emesis.

Sujets

• Metoclopramide
• Microcrystalline cellulose

Informations

• Publié par: erevistas
• Publié le: 01 janvier 2011
• Nombre de lectures: 78

Extrait

REVISTA CIENTÍFICA
Ars Pharmaceutica
Ars Pharm. 2011; 52(3)
FACULTAD DE FARMACIA. UNIVERSIDAD DE GRANADA. ESPAÑA
Editorial»
Martínez-Martínez F, Faus MJ, Ruiz-López MD.
Originales
Development and characterization of antibiotic orodispersible tablets»
Kanani R, Rajarajan S, Rao P.
Simultaneous RP-HPLC method for the stress degradation studies of atorvastatin »
calcium and ezetimibe in multicomponent dosage form
Rajasekaran A, Sasikumar R, Dharuman J.
Hydrophilic polymers as release modifers for primaquine phosphate: Effect of »
polymeric dispersion
Sant S, Swati S, Awadhesh K, Sajid MA, Pattnaik GD, Tahir MA, Farheen S.
Rapidly Disintegrating Tablets of Metoclopramide Hydrochloride Using Novel »
Chemically Modifed Cellulose
Aloorkar NH, Bhatia MS.
Especial
Categorización de las farmacias españolas según la teoría de difusión »
de las innovaciones de rogers en relacion a la práctica del seguimiento
farmacoterapéutico
Casado de Amezúa MJ, Martínez-Martínez F, Feletto E, Cardero M, Gastelurrutia MA.
Utilización terapéutica de los anticuerpos monoclonales»
García Ramos SE, García Poza P, Ramos Díaz F. Ars Pharmaceutica
Rapidly disintegrating tablets of metoclopramide
hydrochloride using novel chemically modifed cellulose
1 2Aloorkar NH , Bhatia MS .
1. Department of Pharmaceutics, Satara College of Pharmacy, 2. Department of Pharmaceutical chemistry, Bharati Vidyapeeth
College of Pharmacy.
Original Paper ABSTRACT
Artículo Original
The purpose of the study was to modify cellulose using hydrochloride salt of 2-aminoethanoyl chloride with
optimum hydrophilic and hydrophobic properties to impart it a superdisintegrant activity and also to formulate Correspondence: N.H. Aloorkar,
and evaluate rapidly disintegrating tablets of metoclopramide hydrochloride using this novel chemically Department of Pharmaceutics,
Satara College of Pharmacy, modifed cellulose. A novel polymer, chemically modifed cellulose was synthesized by chemically modifying
Plot Nº. 1539, Behind Spicer India Ltd., microcrystalline cellulose with hydrochloride salt of 2-aminoethanoyl chloride. The formation of novel polymer
New additional M.I.D.C.,
was confrmed by Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy and
Degaon, Satara, 415 004, Maharashtra, India.
by differential scanning calorimetric (DSC) and elemental analysis. The toxicity study proved the novel modifed Phone: [phone]
cellulose to be non toxic. Rapidly disintegrating tablets of metoclopramide hydrochloride were prepared using e-mail: [e-mail]
novel modifed cellulose and compared for the release of drug with control formulation, prepared using non
Received: 13.04.2010
modifed microcrystalline cellulose. The tests like wetting time, water absorption ratio and in vitro disintegration
Accepted: 05.05.2011
time were carried out to elucidate the relationship between them. The study revealed that novel modifed
cellulose in a concentration of 2% released the drug faster than at a concentration higher than that. Hence it could
be concluded that microcrystalline cellulose, a polymer which is devoid of superdisintegrant activity, can suitably
be modifed by controlled chemical modifcation of it with hydrochloride salt of 2-aminoethanoyl chloride or
similar groups with optimum hydrophilicity and hydrophobicity to convert it into a superdisintegrant material.
It can also be concluded that rapidly disintegrating tablets of metoclopramide hydrochloride can suitably be
developed for the effcient management of emesis.
KEY WORDS: Chemically modifed cellulose, Microcrystalline cellulose, Metoclopramide hydrochloride,
Rapidly disintegrating tablets, Superdisintegrant.
RESUMEN
The purpose of the study was to modify cellulose using hydrochloride salt of 2-aminoethanoyl chloride with
optimum hydrophilic and hydrophobic properties to impart it a superdisintegrant activity and also to formulate
and evaluate rapidly disintegrating tablets of metoclopramide hydrochloride using this novel chemically
modifed cellulose. A novel polymer, chemically modifed cellulose was synthesized by chemically modifying
microcrystalline cellulose with hydrochloride salt of 2-aminoethanoyl chloride. The formation of novel polymer
was confrmed by Fourier Transform Infrared (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy and
by differential scanning calorimetric (DSC) and elemental analysis. The toxicity study proved the novel modifed
cellulose to be non toxic. Rapidly disintegrating tablets of metoclopramide hydrochloride were prepared using
novel modifed cellulose and compared for the release of drug with control formulation, prepared using non
modifed microcrystalline cellulose. The tests like wetting time, water absorption ratio and in vitro disintegration
time were carried out to elucidate the relationship between them. The study revealed that novel modifed
cellulose in a concentration of 2% released the drug faster than at a concentration higher than that. Hence it could
be concluded that microcrystalline cellulose, a polymer which is devoid of superdisintegrant activity, can suitably
be modifed by controlled chemical modifcation of it with hydrochloride salt of 2-aminoethanoyl chloride or
similar groups with optimum hydrophilicity and hydrophobicity to convert it into a superdisintegrant material.
It can also be concluded that rapidly disintegrating tablets of metoclopramide hydrochloride can suitably be
developed for the effcient management of emesis.
PALABRAS CLAVE: Chemically modifed cellulose, Microcrystalline cellulose, Metoclopramide
hydrochloride, Rapidly disintegrating tablets, Superdisintegrant.
26 Ars Pharm. 2011; 52(3): 26-34.Rapidly Disintegrating Tablets of Metoclopramide Hydrochloride Using Novel Chemically Modifed Cellulose
INTRODUCTION administration. It has a short biological half life (3-5 h)
and is usually administered in a dose of 10-15 mg four In the past one decade, there has been an enhanced demand
times a day. A conventional oral administration has good for more patient friendly and compliant dosage forms. As
absorption (>90%) but is extensively metabolized by the liver a result, the demand for developing new technologies
20-22(0-68%) . Hence, this drug was selected as a candidate has been increasing annually. Since the development
drug to formulate a rapidly disintegrating dosage form cost of a new drug molecule is very high, efforts are now
using the novel superdisintegrant, cellulose chemically being made by pharmaceutical companies to focus on the
modifed with hydrochloride salt of 2-aminoethanoyl development of new drug dosage forms for existing drugs
chloride (1% substitution). with improved safety and effcacy together with reduced
dosing frequency, and the production of more cost effective The present study was aimed to formulate and evaluate
1dosage forms . rapidly disintegrating tablets of metoclopramide
hydrochloride and also to evaluate chemically modifed Many patients fnd it diffcult to swallow tablets and hard
cellulose for its possible superdisintegrant activity.gelatin capsules; consequently they do not take medication
as prescribed. It is estimated that 50% of the population is
affected by this problem which results in a high incidence MATERIALS AND METHODS
2,3of incompliance and ineffective therapy . Hence the
Materials
development of an orally disintegrating tablet or rapidly
Microcrystalline cellulose, hydrochloride salt of 2- disintegrating tablet (RDT) has attracted not only the
4 aminoethanoic acid and vanilla favor were procured pharmaceutical industry, but also the academia .
from Rajesh Chemicals (Mumbai, India). Metoclopramide RDTs are preferred by an increasing number of patients
hydrochloride was supplied as the gift sample by Mediorals especially children and elderly, but also adult consumers
Pvt. Ltd. (Satara, India). Spray dried lactose was supplied who like to have their medication readily available at any
by Medule Pharma (Goa, India). All the other chemicals time5. This dosage form is also suitable for those who
used were of analytical grade and were used as procured.are suffering from dysphagia and thus lead to improved
6patient compliance .
Experimental Design
RDTs are useful in bedridden or developmentally Modifcation of microcrystalline cellulose with
disabled patients who may face problems in swallowing hydrochloride salt of 2- aminoethanoyl chloride (1%
conventional tablets or capsules and liquid orals or syrups substitution): A molar ratio of microcrystalline cellulose
leading to ineffective therapy, with persistent nausea, to salt of 2-aminoethanoyl chloride was
sudden episodes of allergic attacks or coughing for those computed on the basis of molecular weight, number of
who have an active life style. RDTs are also useful when monomers, and free hydroxyl groups present in each
local action in oral cavity is desirable such as local anesthetic monomer of microcrystalline cellulose and a molar ratio
7-13for toothaches, oral ulcers, cold sores or teething . Recent of 1% substitution of microcrystalline cellulose with
developments in rapidly disintegrating tablets provide a hydrochloride salt of 2-aminoethanoyl chloride was
convenient