DEVELOPMENTAND EVALUATION OF ANTIAMOEBIC MICROPARTICLES
M.PHARM DISSERTATION PROTOCOL
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
N.M.VISWANATH
I M.PHARM
UNDER THE GUIDANCE
MRS.BENY BABY
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
BENGALURU-560064
(2010-11)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA, BENGALURU.
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1 /Name of the Candidate and Address
/ N.M.VISWANATHKarnataka College of Pharmacy
# 33/2 Thirumenahalli
Hegde Nagar Main Road
Bengaluru-560064.
PERMANENT ADDRESS
S/o N.R.Manjunath
sri vasavi general traders
D.no.17-3-566 main bazaar
Hindupur,Anantapur (Dist)
ANDHRAPRADESH.
2 / Name of the Institution / Karnataka college of pharmacy
# 33/2 Thirumenahalli
Hegde Nagar Main Road
Bengaluru-560064.
3 / Course of the Study and Subject /
MASTER IN PHARMACY(PHARMACEUTICS)
4 /Date of Admission
/ 7thJULY- 20105 / Title of the Topic
DEVELOPMENT AND EVALUATION OF ANTIAMOEBIC MICROPARTICLES
6.
6.1
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6.2
6.3 / Brief Resume of the Intended Work
Need for the study
Microparticles are the particles range from 1to1000 μm size of active principle (drug or biologically active material). A microparticle is a structure made of a continuous phase of one or more miscible polymers in which particulate drug is dispersed at either the macroscopic or molecular levels,which are stable, solid, polymeric particles that can incorporate drugs either inside them or bound to the polymeric matrix. They are made of biodegradable polymers of natural or synthetic origin, that are degraded in vivo enzymatically, non-enzymatically or by a combination of both to give non-toxic products that are readily eliminable by the organism through the usual metabolic routes1.
They offer versatility for drug administration as they can be formulated as solutions, suspensions, emulsions, self-emulsifying systems and microemulsions and it can be prepared as unit dose forms such as sealed hard or soft gelatin capsules. However difference between the two system is the nature of the microparticle matrix in which no well defined wall or envelope exists.
Microparticles have been widely accepted as a means to achieve oral and parenteral controlled release. It not only reduces the dose of the drug,reduces the gastric irritation reaching to the effective biological sites rapidly but also results in reduced toxicity of the targeting.A number of different substances both biodegradable as well as non-biodegradable have been investigated for the preparation of microparticles.
But in the past few years, pharmacists have been focused their research in colloidal drug delivery system/colloidal carriers, like liposomes, microspheres,microparticles and nanoparticles as a targeting carriers, which has given selective targeting. Microparticles based on polymers are frequently employed as drug delivery systems to achieve a sustained / controlled release and site specific targeting of the incorporated drug.
Antiamoebics are the drugs of choice for the treatment of amoebic infections due to several anaerobic organisms like fusobacterium, helicobacter pylori, clostridium perfringens produces ameobisis, giardiasis, trichomoniasis. Antiamoebics produces action entering the cell by diffusion its nitro group .The nitro radical acts on the sink which competes with biological electron acceptors of anaerobic microorganism. The energy metabolism of anaerobes is disrupted.
The main aim of the present work is to develop the antiameobic microparticles by using a polymer for prolonged release, to reduce the dose of the drug, to reach to the effective biological sites rapidly but also results in reduced toxicity of the targeting with relatively constant effective level of drug .It is evident that a promising controlled release microparticulate drug delivery of antiamoebics can be developed.
Review of the literature
Tripathi KD2 The drug has selected as a antiamoebic drug in Essential medical pharmacology and the drug of the antiamoebic is studied as its properties molecular weight, half life and bioavailability.
George M etal3Nonreplicating antigens are poorly immunogenic when given orally, Studies in laboratory animals have clearly demonstrated that microparticles can significantly improve the immunogenicity of orally administered antigens. This article the progress in oral microparticle antigen delivery are reviewed possible, studies in humans and large animals are highlighted. In addition possible approaches that have the potential to significantly improve microparticle delivery of oral vaccines are suggested.
Ravi Kumar Reddy J etal4Formulate delayed release Metronidazole microparticles, which will have enteric as well as sustained release properties. For the preparation of Metronidazole microparticles CAP, HPMCP, Eudragit L-100 and Eudragit S-100 were used as coating materials. Microparticles of Metronidazole were prepared using cellulose acetate phthalate as the retardant polymer by emulsion-solvent evaporation method. The microparticles formed were collected by filtration. Drug content and percentage of drug entrapment were found to good in all the batches, as the entrapment values were not less than 85%. All batches of microparticles were found to have enteric release property as it was expected.
Mladenovska K etal5Chitosan-Ca-alginate microparticles for colon-specific delivery and controlled release of 5-aminosalicylic acid after peroral administration were prepared using spray drying method followed by ionotropic gelation/polyelectrolyte complexation. 1H NMR, FTIR, X-ray and DSC studies indicated molecularly dispersed drug within the particles with preserved stability during microencapsulation and in simulated in vivodrug release conditions. The diffusional exponents according to the general exponential release equation indicated anomalous (non-Fickian) transport in 5-
ASA release controlled by a polymer relaxation, erosion and degradation. Biodistribution studies of [131I]-5-ASA loaded chitosan-Ca-alginate microparticles, carried out within 2 days after peroral administration to Wistar male rats in which TNBS colitis was induced, confirmed the dominant localization of 5-ASA in the colon with low systemic bioavailability.
Ilica DR et al6Drug-free microparticles were prepared using spray congealing process with the intention of studying the influence of processing parameters. In addition, microparticles with glimepiride, a model poorlywater-soluble drug,were preparedby spray congealing using three different hydrophilic meltable carriers: GelucireR 50/13, poloxamer 188, and PEG 6000. Spherical microparticles with relatively smooth surface were obtained, with no drug crystals evident on the surfaces of drug-loaded microparticles. XRPD showed no change in crystallinity of the drug due to the technological process of microparticle production. All glimepiride-loaded microparticlesshowed enhanced solubility compared to pure drug.
Alflamprecht et al7A multiple unit dosage form for oral delivery based on the microencapsulation of anti-inflammatory drugs using different biodegradable polymers, poly(e-caprolactone), polylactic acid and poly(lactic-co-glycolic acid), prepared either by the water-in-oil-in-water (w/o/w) or the solid-in-oil-in-water (s /o/w) solvent evaporation method was developed. The physical state of drugs and polymers was determined by differential scanning calorimetry (DSC), imaging of the particles was performed by scanning electron microscopy and confocal laser scanning microscopy.. In vitro release studies showed a controlled release of sulfasalazine and betamethasone from microparticles prepared by the s /o/w-method; a pronounced burst release of sulfasalazine was observed from microparticles prepared by the w/o/w-method.
Cui-Yun Yet al8Microparticle protein delivery systems based on calcium alginate were fabricated using a very convenient method, i.e. directly shredding the protein-loaded calcium alginate beads into microparticles in a commercial food processor for 3 min. This fabrication method offered high encapsulation efficiency and a high particle yield.Compared with beads, the microparticles exhibited a faster release rate in the initial release stage.By comparing the release profiles of uncoated beads/microparticles and chitosan-coated beads/microparticles,it was found that the releases from chitosan-coated beads/microparticles were slower.
Tua J etal9A spray–coagulation method was developed for the preparation of large scale of porous alginate microparticles. The effect of three variables on porosity was evaluated: (1) alginate solution concentration (2) the concentration of CaCl2 in the coagulation medium and (3) the ratio of guluronic acid to manuronic acid of the alginate. Methylene blue (MB), a highly water-soluble compound and a practically water-insoluble compound, 4-phenylazoaniline (PAA) were used as the model drugs to study drug loading and release characteristics from alginate microparticles. The results indicated that (1) porous alginate microparticles can be produced by the spray–coagulation method; (2) drugs can be loaded by the adsorption method; (3) and the obtained microparticles maybe used for delaying the release of drugs of low water solubility in acidic conditions
Kashappagoud HD10 Has studied on preparation and characteristics of high amylose corn starch/pectin blend microparticles by usingcross-linking method.Cross linking method has been applied to HACS and extensively studied for the controlled drug release applications. The process involving simple preparative procedures are preferred for the preparation of sustained release carriers in the pharmaceutical industries. Spray drying microencapsulation technique is widely used in the pharmaceutical industries because of its numerous advantages over other microencapsulation methods.The advantage of spray drying technique for application to microencapsulation is that it is reproducible, rapid, and easy to scale up. Therefore, this paper describes the preparation of new blend microparticles by spray drying technique and their characteristics size, surface morphology, and in vitro drug release profile.
Baras B et al11Microparticles were produced by spray-drying from high molecular weight polylactide (PLA R207) for the development of long-lasting controlled release systems of vaccines, which may be designed to obviate the need for booster doses. The BSA release rate from microparticles varied from 11.1792.20 to 92.6093.46% in 24 h. This burst release was followed by a BSA release rate slower for microparticles with a low BSA loading. Moreover, the increase of the R207 concentration resulted in a decrease of the BSA release rate while the burst release was not modified.
Gowda DV et al12The aim of the present study was to prepare and evaluate microparticles of Indapamide using blend of HPMC and Ethyl Cellulose by Spray drying technique for controlled release. Sieve analysis data indicated that the prepared microparticles were in the ranges of 265 $m to 187$m. DSC studies and FT-IR spectra showed that the encapsulated drug was stable in the prepared formulations. The prepared formulations were analyzed quantitatively for the amount of encapsulated drug. From the drug loading, encapsulation efficiency and in vitrodrug release data,was selected as optimized formulation.
Helmut R et al13To investigate the potential of physiological lipids as an alternative to synthetic polymeric materials such as poly(lactide–co-glycolide), peptide-containing glyceryl tripalmitate microparticles were prepared and without the use of organic solvent were employed. Thymocartin (TP-4), an immunomodulating tetrapeptide and insulin were chosen as model peptides and incorporated as a solid or dissolved in aqueous solution. The resulting microparticles were characterized with respect to particle size and morphology, biocompatibility, drug content (encapsulation efficiency) and in vitro release behavior. The in vitro release behavior was substantially influenced by the physicochemical properties of the model peptides used in this study.
Lutfi G et al14Prolonged release microparticles were prepared using polymer by spray-drying and casting-drying techniques. For the characterization of those microparticles in vitro dissolution from the microparticles were performed. HPLC was used for the assay method and was validated. All the formulations obtained showed prolonged release when compared to pure drug. Microparticles prepared by methods have difference in their release.
Lai Y et al15 Characterize and evaluate the stability of a model enzyme, acid phosphatase, in albumin microsphere method mini spray dryer (Buchi 191) with a high efficiency cyclone,the particle sizes and zeta potential of the microparticles were evaluated using a laser particle counter. Stability of the formulation was evaluated and performed to evaluate any unfolding events that may have occurred after the spray drying process.
Objective of the Study
The objective of the study is as follows
- To develope Microparticles as Drug Carrier System
- To formulate a suitable method for Microparticles
- Characterization of formulated Microparticles
- Evaluation of formulated Microparticles
- Stability studies for the selected formulations as per ICH guidelines
7
7.1
7.2
7.3 / Materials and Methods
Source of data
. Review of literature resourced from
Journal such as
. Indian journal of pharmaceutical sciences
. Journal of controlled release
. Indian drugs
. Science direct
Websites:
. Word Wide Web
. J-Gate@Helinet
Method of collection of data (including sampling procedures if any)
The data will be collected from prepared formulations subjected to
different evaluation techniques, scale-up techniques and stability studies
obtained from ICH guidelines.
Materials
Antiamoebic drug and bases will be procured / obtained from pharma grade
suitable manufacturer. All the other reagents will be of analytical grade.
7.4
7.5
7.6 / Methods
1) Preformulation Studies
a) Thermal Analysis
b) Incompatability Studies
2) Formulation Studies
a) Spray Drying
b) Freeze Drying
c) Polymerization
3) Characterisation of Microparticles
a) Surface Morphology
b) Particle Size Analysis
4) Evaluation of Microparticles
a) Drug Loading Efficacy
b) Content Uniformity
c) Assay
d) Invitro Drug Release Studies
5) Stability Studies as per ICH guidelines
Does the study require any investigation or interventions to be
conducted on patients or other humans or animals?
NOT APPLICABLE
Has ethical clearance been obtained from your institution in case of 7.5?
-NO-
8 / List of References
- Chien YW. Rate-controlled Drug Delivery Systems. Ind J Pharm Sci 1988; Mar-Apr: 63-5.
- Tripathi KD.Antiamoebic drugs. Essentials of Medical Pharmacology. 6th ed. India:Jaypee; 2008. p.797-8.
- George M, Terry LB, Lorne AB.Microparticles for oral delivery of vaccines. Expert Opin Drug Deliv2005;2(5):791-806.
- Ravikumar RJ, Gnanaprakash K, Badarinath AV, Madhusudhana C. Formulation and evaluation of microparticles of metronidazole. J Pharm Sci Res 2009;1(x):131-6.
- Mladenovska K, Raicki RS, Janevik EI , Ristoski T, Pavlova MJ, Kavrakovski Z, Dodov MG, Goracinova K .Colon-specific delivery of 5-aminosalicylic acid from chitosan-ca-alginate microparticles. Int J Pharma 2007;(342):124-36.
- Ilica I, Dreu R, Burjakb M, Homarb M, Kerca J, Srcica S. Microparticle size control and glimepiride microencapsulation using spray congealing technology.Int J Pharma2009;(381):176-83.
- Alf L, Helana RT, Ulrich S, Clausmichael L. Biodegradable microparticles as a two-drug controlled release formulation: a potential treatment of inflammatory bowel. J Control Release 2000;69:445-54.
- Cui-Yun Y, LHJ, Si-Xue C, Xian-Zheng Z and Ren-Xi Z. Fabrication of microparticle protein delivery systems based on calcium alginate.J Microencapsul2010;2(27):171-7.
- Tu J, Bolla S, Barr J, Miedemab J, Lia X, JastiB.Alginate microparticles prepared by spray–coagulation method:Preparation, drug loading and release characterization.
- Desai, KGH. Preparation and Characteristics of High Amylose Corn Starch/ Pectin Blend Microparticles: A Technical Note.AAPS PharmSciTech 2005 Mar 3;1-21.
- Baras B, Benoit MA, Gillard J. Parameters influencing the antigen release from spray-dried poly(DL-lactide) microparticles.Int J Pharma2000;(200):133-45.
- Gowda DV, Khan MS and Nagendra R. Spray dried indapamide microparticles for controlled release– a novel approach. Int J Pharm and Bio Sci 2010Oct-Dec;1(4):459-66.
- Helmut R,Joachim H, Achim G. Lipid microparticles as a parenteral controlled release device for peptides. J Control Release 2001;73:339-50.
- Lutfi G,Muzeyyen Dand Yasemin Y. Preparation of Prolonged Release Clarithromycin Microparticlesfor Oral Use and Their In Vitro Evaluation. Arch Pharm Res 2006;29(10):921-7.
- LaiY,Cotta K,SouzaDM.Characterization and stability studies of acid phosphatase bovine serum albumin microparticles.
9 / Signature of the Candidate / (N.M.VISWANATH)
10 / Remarks of the Guide / The topic selected for dissertation is satisfactory. Adequate equipments and chemicals are available to carry out the project work.
11 / Name and Designation
11.1 / Guide / MRS.BENY BABY
ASST.PROFESSOR
DEPT. OF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BENGALURU-64
11.2 / Signature of Guide / (MRS.BENY BABY)
11.3 / Co-Guide / NOT APPLICABLE
11.4 / Signature of Co- Guide / NOT APPLICABLE
11.5 / Head of the Department / DR.K. RAMESH
PRINCIPAL AND HOD OF PHARMACEUTICS
DEPARTMENT OF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BENGALURU-64
11.6 / Signature of HOD / (DR. K.RAMESH)
12 / 12.1 / Remarks of the principal / All the required facilities will be providedto carry out dissertation work under the supervision of theguide.
12.2 / Principal / DR.K. RAMESH
PRINCIPAL
KARNATAKACOLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BENGALURU-64
12.3 / Signature of the Principal / (DR.K. RAMESH)
1