Download ENCLOSURE – I 6) BRIEF RESUME OF THE INTENDED WORK 6.1

ENCLOSURE – I
6) BRIEF RESUME OF THE INTENDED WORK
6.1) NEED FOR THE STUDY
Azithromycin (AZI) is a semi-synthetic, acid stable erythromycin derivative. It
plays a leading role in the treatment or prophylaxis of common respiratory tract
infections, skin infection and several other clinical diseases, such as opportunistic
infections in AIDS, toxoplasmosis, paediatric infections, urethritis, middle ear infections,
tonsillitis, throat infections, laryngitis, bronchitis, pneumonia and sinusitis etc. However,
the clinical application of azithromycin is limited by its low bioavailability as a result of
its poor solubility in water and poor gastrointestinal response1. And, oral treatment of this
drug is often associated with various adverse effects related to the gastrointestinal tract
cramping, diarrhoea, nausea abdominal pain and vomiting2.
Microencapsulation for oral use has been employed to sustain the drug release,
and to reduce or eliminate gastrointestinal side effects3. In addition, multiparticulate
delivery systems spread out more uniformly in the gastrointestinal tract. Various
swellable polymers, hydrophobic polymers etc., are used frequently as matrices or
coating materials for sustained or controlled release dosage forms4,5. Hence the present
study is undertaken to formulate microspheres of azithromycin by using various polymers
to achieve controlled release which may result in lower gastrointestinal side effects of the
drug. Further it is planned to study the various factors influencing the release of drug
from the microspheres such as biodegradation kinetics of the polymers, polymer
molecular weight, polymer to core ratio etc.
ENCLOSURE – II
6.2) REVIEW OF LITERATURE
Zhang Z et al6 prepared and evaluated azithromycin (AZI) microcapsules based
on hollow polyelectrolyte (PE) microcapsules by layer-by-layer self-assembly onto the
surface of silica microsphere (SiO2). The prepared AZI/PE microcapsules with an
average diameter 1.2m possessed homogeneous size and regular spherical shape. FTIR
spectra and XRD patterns indicated that AZI molecular structure was not changed and
AZI crystal state changed from monohydrate to dihydrate. The drug invitro release
experimental results showed an obvious improvement in the dissolution rate of the
prepared AZI/PE microcapsules in comparing with AZI raw material drug powder.
Gao Y et al7 prepared and studied microspheres of roxithromycin with eudragit
S100 and silica by the emulsion solvent diffusion method to mask the bitter taste of the
antibiotic. The effect of different polymers and drug–polymer ratios on the taste masking
and the characteristics of the microspheres were investigated. It was found that Eudragit
S100 was the best for masking the unpleasant taste of roxithromycin among the six kinds
of
polymers
investigated.
The
influence
of
other
formulation
factors,
i.e.
dichloromethane–acetone ratios and silica–polymer ratios on the properties of the
microspheres were also examined.
Ganza-Gonzaalez A et al8 designed and investigated the usefulness of chitosan
and chondroitin sulphate microspheres for oral controlled release of metoclopramide
hydrochloride in oral administration. Microspheres were prepared by spray drying of
aqueous polymer dispersions containing the drug and different amounts of formaldehyde
as cross-linker. Drug release kinetics was investigated in vitro in media of different pH.
Chondroitin sulphate microspheres scarcely retarded drug release, regardless of crosslinker concentration and medium pH, and were thus not further characterized. Chitosan
microspheres prepared with more than 15% formaldehyde (w/w with respect to polymer)
showed good control release (more than 8 h), and release rates were little affected by
medium pH. Release from chitosan microspheres prepared with 20% formaldehyde was
independent of pH, suggesting that this may be the most appropriate formulation. The
kinetics of drug release from chitosan microspheres were best fitted by models originally
developed for systems in which release rate is largely governed by rate of diffusion
through the matrix.
Rastogi R et al9 studied isoniazid (INH) microspheres produced by a modified
emulsification method using sodium alginate as the hydrophilic carrier. Particle sizes of
both placebo and drug-loaded formulations were measured by SEM and the particle size
distribution was determined by an optical microscope. The physical state of the drug in
the formulation was determined by DSC. The release profiles of INH from microspheres
were examined in simulated gastric fluid (SGF pH 1.2) and simulated intestinal fluid (SIF
pH 7.4). Gamma-scintigraphic studies were carried out to determine the location of
microspheres on oral administration and the extent of transit through the gastrointestinal
tract (GIT). Concentration of the cross-linker up to 7.5% caused increase in the
entrapment efficiency and the extent of drug release. Optimized isoniazid-alginate
microspheres were found to possess good bioadhesion (72.25±1.015%). The bioadhesive
property of the particles resulted in prolonged retention in the small intestine.
Microspheres could be observed in the intestinal lumen at 4 h and were detectable in the
intestine 24 h post-oral administration, although the percent radioactivity had
significantly decreased (t1/2 of 99mTc = 4–5 h).
Sinduri P and Purushotaman M10 prepared and evaluated norfloxacin sustained
release microspheres using various polymers like carbopol 934, sodium carboxy methyl
Cellulose in different drug:polymer ratios by using multiple emulsion solvent evaporation
technique. Microspheres were evaluated for parameters like angle of response, bulk
density, particle size, drug content in microspheres, drug loading, encapsulation
efficiency and Invitro drug release studies. The prepared microspheres of norfloxacin
showed sustained release of drug from the formulation for a period of 12 hours.
ENCLOSURE-III
6.3) OBJECTIVES OF THE STUDY
The present work is planned with the following objectives:
•
To prepare microspheres containing azithromycin by suitable microencapsulation
technique using different polymers.
•
To evaluate the prepared microspheres for drug content, encapsulation efficiency,
surface morphology by SEM analysis, size analysis, swelling property and in vitro
drug release studies.
•
To investigate the possibility of interaction between the combination of polymers
and also between polymers and drugs by FTIR.
•
To study the effect of different compositions of polymers on the drug release
profile.
ENCLOSURE – IV
7) MATERIALS AND METHODS
7.1) SOURCE OF DATA
The primary data will be collected by conducting various experiments and
investigations in the laboratory and recording the observations. The secondary data
will be collected by referring various national and international journals, books,
Pharmacopoeia’s and professional websites like Helinet, Pubmed etc.
ENCLOSURE–V
7.2) METHOD OF COLLECTION OF DATA
1. Instruments like dissolution apparatus, UV spectrophotometer will be used to record
the observations.
2. Drug-polymer interaction will be investigated by using analytical techniques such
as DSC, FT-IR etc.
3. Various polymers (hydrophilic and hydrophobic) such as chitosan, carbopol 934,
eudragit RL 100, eudragit RS 100, ethyl cellulose, carnauba wax etc., will be used to
fabricate microspheres containing the model drug in different drug:carrier ratios by
adopting suitable techniques.
4. The prepared microspheres shall be characterized for their physicochemical
properties using standard techniques.
5. In vitro release profiles of drug in simulated physiological fluid will be studied
using USP dissolution apparatus. The in vitro data shall be analysed statistically and
kinetics of drug release shall be studied.
ENCLOSURE –VI
8) LIST OF REFERENCES
1. Zhang DR, Tan TW, Gao L, Zhao WF, Wang P. Preparation of azithromycin
nanosuspensions by high pressure homogenization and its physicochemical
characteristics studies, Drug Dev Ind Pharm 2007;33:569-575.
2. Dunn CJ, Barradell LB. Azithromycin: a review of its pharmacological properties and
use as 3-day therapy in respiratory tract infection. Drugs 1996;51:483-505.
3. Kondo A. Microcapsule Processing and Technology, Marcel Dekker, New York, NY,
1979.
4. Harland RS, Gazzaniga A, Sangalli ME, Colombo P, Peppas NA. Drug/polymer
matrix swelling and dissolution. Pharm Res 1988;5:488-494.
5. Chitnis VS, Malshe VS, Lalla JK. Bioadhesive polymers-synthesis, evaluation and
application in controlled release tablets. Drug Dev Ind Pharm 1991;71:879-892.
6. Zhang Z, Zhu Y, Yang X, Li C. Preparation of azithromycin microcapsules by a
layer-by-layer self-assembly approach and release behaviors of azithromycin.
Colloids and Surfaces A: Physicochem Eng Aspects 2010;362:135-139.
7. Gao Y, Cui F, Guan Y, Yang L, Wang Y, Zhang L. Preparation of roxithromycinpolymeric microspheres by the emulsion solvent diffusion method for taste masking.
Int J Pharm 2006;318:62-69.
8. Ganza-Gonzaalez A, Anguiano-Igea S, Otero-Espinar FJ, Blanco Meandez J.
Chitosan and chondroitin microspheres for oral-administration controlled release of
metoclopramide. Eur J Pharm and Biopharm 1999;48:149-155.
9. Rastogi R, Sultana Y, Aqil M, Ali A, Kumar S, Chuttani K, Mishra AK. Alginate
microspheres of isoniazid for oral sustained drug delivery. Int J Pharm 2007;334:7177.
10. Sindhuri P, Purushotaman M. Formulation and evaluation of norfloxacin
microspheres using different polymers. Int J Pharm & Ind Res 2011;1(1):32-35.