FORMULATION AND EVALUATION OF ANTI-FUNGAL
SOLID LIPID MICRO/NANOPARTICLES
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
NIZAMUDDIN
I M.PHARMACY
UNDER GUIDANCE OF
MR.S.RAJARAJAN
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
KARNATAKA COLLEGE OF PHARMACY
BENGALURU-560064
(2012-2013)
RAJIVGANDHI UNIVERSITY OF HEALTH SCIENCE
KARNATAKA, BENGALURU.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
Name of the Candidate and Address
/ NIZAMUDDINKarnataka college of Pharmacy
# 33/2 ThirumenahalliHegdenagar, main road
Bengaluru-560064.
PERMANENT ADDRESS
S/O: Md.Murtuza
Vill: Fakirana Tola, Post: Tehwara
Via: Singhwara, Thana: Katra
Dist: Muzaffarpur, State: Bihar-847106
Name of the Institution
/Karnataka college of Pharmacy
# 33/2 Thirumenahalli, Hegdenagar main road Bengaluru-560064Course of Study and Subject
/MASTER OF PHARMACY
IN PHARMACEUTICAL TECHNOLOGYDate of the Admission
/ 08/01/ 2013Title of the Topic
FORMULATION AND EVALUATION OF ANTI-FUNGAL
SOLID LIPID MICRO/NANOPARTICLES
Brief resume of the intended work:
6.1 Need for the study:
Lipid based drug delivery system such as liposome, microparticles and nanoemulsion, self emulsified drug delivery system and solid lipid micro/nanoparticle are become more popular because lipid materials are easily characterized contain a high range of well defined/tolerated surfactant molecule and can be developed for several administration route in recent days.
Lipids particle (LPS) can be used as penetration enhancer of encapsulated drug through the skin because of their excellent occlusive and hydrating property.
Lipid-based delivery systems are an accepted, proven, commercially viable strategy to formulate pharmaceuticals and considerations of cost, product stability, toxicity, and efficacy. Lipid-based formulations have traditionally been to improve the solubility of sparingly soluble drugs.The observation that particulates such as “long-circulating” emulsions and liposome’s can “passively” accumulate at sites of disease or inflammation provides a strong rationale for using lipid-based systems to increase drug bioavailability at the disease site. Infact SLM is biodegradable, chemically stable. Microparticles able to incorporate high amounts of Lipophilic drugs.
SLM can be administered by subcutaneous, oral, IM, topical or pulmonary ways, but SLM suffered from a low resistance to heat, shoe some physical instability and early burst release of encapsulated drugs (proteins or water insoluble drugs). The SLM have advantages that include good affinity for stratum corneum.
Solid Lipid Nanoparticle (SLN) are sub-micron colloidal carrier which is composed of physiological Lipid, dispersed in water or in an aqueous surfactant solution and offer unique properties such as small size, large surface area, high drug loading and the interaction of phases at the interfaces, and are attractive for their potential to improve performance of pharmaceuticals, neutraceuticals and other material.
Invasive fungal infections are progressive, life-threatening infections, a leading cause of morbidity and mortality in immune compromised patients. Most of the anti-fungal drugs are having low bioavailability because of its insolubility in water and some gastrointestinal factors like intestinal metabolism so overcome to this problem drug is formulated in micro/nanoparticle in order to increase dissolution rate and good oral bioavailability.
Endeavor of this formulation is to evaluate and increase the bioavailability of the anti-fungal drug belonging to BSC class ii. The systems were mainly to investigate on the basis of their physicochemical properties, in vitro release and stability studies.
6.2 review of the literature:
· New solid lipid microparticles were formulated for controlled ibuprofen release using hot melt dispersion method. New sustained release ibuprofen composite microparticles of a solid lipid at ambient temperature, cetyl alcoholwer prepared. Hydrophobic aerosol® r974 allowed the formation of homogeneous microparticles. However, SLM obtained differ from Pickering emulsions because silica, particularly by using aerosil® r974 is not only adsorbed onto the interface between ca and water, but diffuse inside the lipid core of microparticles owing to hydrophobic forces to form a homogeneous composite core.1
· Solid lipid microparticles and solid lipid nanoparticle can be produced to incorporate hydrophilic and hydrophobic proteins and seems to fulfill the requirements for an optimum particulate carrier system. Protein and antigens intended for therapeutics preparation may be incorporated or adsorbed onto SLN and further administered by parenteral routes or by alternatives routes2.
· Solid lipid microparticles loaded with Ketoprofen were prepared by using single emulsion – solvent evaporation method, in which glycerylmonosterate and tween 80 were incorporated. Solid lipid microparticles characterization was made by scanning electron microscope were particles was found to be spherical in shape. Entrapment efficiency and drug loading capacity was found to be 72.60 ±1.6%, 17.98 ±0.7 %3.
· Solid lipid microparticles (SLM) loaded with the sun screen agent, octyl-dimethylaminobenzoate (ODAB), were prepared in order to achieve enhanced sunscreen photo stability. The microparticles were produced by melt dispersion technique using glycerylbehenate as lipid material and poloxomer 188 as an emulsifier. The SLMs achieved a reduction of sunscreen photo degradation in the hydrogel vehicle (ODAB loss is decreased). Therefore, the efficacy of the ODAB-loaded SLMs was markedly affected by the vehicle4.
· Lipid microparticles loaded with the flavonoid, quercetin to enhance its stability in tropical formulation .The microparticles were produced using tristearin as lipid material and Phosptiatidylcholine as emulsifier .The obtained lipoparticles were characterized by release studies scanning electron microscopy and powder X- ray diffractometry. Free or microencapsulated quercetin was introduced in a model cream formulation and irradiated with solar simulator and extent of photo degradation was measured by HPLC5.
· SLMs are prepared by using Hot Air Coating (HAC) technique and used to prepare micro particulate systems containing nifedipine. Binary mixtures constituting of nifedipine and cetearyl alcohol (CA) in different proportions (30:70, 50:50, 70; 30). The operative conditions applied in the spray process allow the obtaining of microparticles containing relevant percentage of drug. The experimental results give evidence that the milling pre-treatment of mixtures, has significant effects on the properties of the lipid coated microparticles6.
· Poorly soluble drug controlled release tablets (SLM) of felodipine were prepared by spray chilling method into solid dispersion microparticles. The microparticles were characterized by FTIR, hot stage microscopy, scanning electron microscopy and image analysis. Felodipine release rate was slowest from the least Lipophilic tablets7.
· The anti-inflammatory Solid lipid microparticles of curcumin for the treatment of inflammatory bowel disease in a colitis induced rat made by a colon specific delivery approach were prepared and evaluated.SLM of curcumin were prepared with various lipids, palmitic acid, steric acid and soya lecithin with optimized percentage of poloxamine 1888.
· Nano-encapsulations were liberated from barley protein microparticles for oral delivery of bioactive compounds. Novel microparticles (3–5µm) were created by pre-emulsifying barley proteins with a homogenizer followed a micro fluidizer system. Degradation and bioactive compound release were studied in the stimulated gastro-intestinal (GI) tract. Data revealed that Nano-encapsulations (20-30nm) were formed as a result of enzymatic degradation of barley protein microparticles bulk matrix in the simulated gastric tract. These microparticles provide new strategy to the development of targeted delivery systems for lipophilic bioactivcompounds9.
· Lectin-modified lipid nanoparticle containing insulin was formulated and to evaluate the potential of the lectin-modified colloidal carriers for oral administration of peptide and protein drugs. For comparison, some insulin-loaded SLNs were modified with WGA-N-glut-PE. The results demonstrated that SLNs and WGA-modified SLNs promoted the oral absorption of insulin10.
· Super paramagnetic iron oxide nanoparticles (SPIONs) are attractive materials that have been widely used in medicine for diagnostic imaging and therapeutic applications. In our study, SPIONs and the corticosteroid Dexamethasone acetate (DXM) are co-encapsulated into PLGA microparticles for treating local inflammatory conditions such as arthritis. The results show that the microparticles have an excellent biocompatibility with synoviocytes and that they are internalized through a phagocytic process. This type of carrier could represent a suitable magnetically retainable intra-articular drug delivery system for treating joint diseases such as arthritis or osteoarthritis11.
· Cidofovir is a new class of antiviral agent with potent in vivo and in vitro activity. Aim of this work is to obtain a prolonged therapeutic effect of drug in basal epidermis after its topical application. For this PLGA microparticles were prepared by using solvent evaporation and spray-drying methods. Drug solution in 0.2% PVA served for comparison. At last concluded that, cidofovir- loaded microparticles could improve cidofovir topical therapy since these vehicles amcreasedd rug retention in the basal epidermis and decreased in penetration through the skin12.
· Cationic polyactide-co-glycolide (PLG) microparticles can be effectively used to adsorb DNA and generate potent immune response in vivo. Cationic PLG microparticles formulations with adsorbed DNA were prepared using a modified solvent evaporation technique. Formulations with a fixed CTAB content and DNA load were prepared13.
· OVA-containing chitosan microparticles (chi-OVA), were prepared, coated with Eudragit L 100 (ER), and evaluated as oral vaccine. They suggested that ER-chi-OVA should be possibly useful to induce an intestinal mucosal immune response14.
6.3 OBJECTIVE OF THE STUDY
The objective of the study is as follows:
1) The current study is to formulate and evaluate Anti-Fungal solid lipid micro/nanoparticle.
2) Formulation of solid lipid micro/nanoparticle by suitable methods.
3) Evaluation of solid lipid micro/nanoparticle for the prepared/ formulated products.
4) In vitro dissolution studies for the prepared/ formulated products.
5) Stability studies as per ICH guide lines.
7. MATERIALS & METHODS
7.1 SOURCE OF DATA
· Review of literature from:
Journals such as:
· International Journal of Pharmacy and Pharmaceutical Sciences.
· International Journal of Pharmaceuticals
· European Journal of Pharmaceutics and Biopharmaceutics
· Biomaterials
· Advance Drug Delivery Review.
Web sites :
· Word wide web.
· Drug bank.com
· Science Direct
7.2 Materials
Anti-Fungal drug and excipients used will be obtained/ procured from Parma grade suitable manufacturer. Other reagents will be of Analytical grade.
7.3 Methods
1)Preparation of solid lipid micro/nanoparticle by
a. Hot Melt Dispersion Method.
b. Melt Dispersion Method.
c. Hot Emulsion Method.
d. Modified Solvent Evaporation Method.
e. Hot Air Coating.
f. Solvent Extraction Process.
2) Evaluation by analytical methods
a. Size and Morphology
b. Particle Size Distribution
c. Scanning Electron Microscope
d. Differential Scanning Colorimetry
e. X-Ray Diffraction.
f. Infra Red Spectroscopy
g. Determination Of Drug Loading.
h. Microparticles Characterization.
I.Invitro Studies.
7.4 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.
7.5 Does the study require any investigation or interventions to be Conducted on patients or other humans or animals?
- NOT APPLICABLE-
7.6 Has ethical clearance been obtained from your institution in case of 7.5? –
- NOT APPLICABLE-
8. LIST OF REFERENCES
1) Robitzer M, Legrand P, Perge L, et al., New solid lipid microparticles for controlled Ibuprofen release: Formulation sand characterization study. Int J Pharm2011; doi:10.1016/j.ijpharm. 2011.10.027.
2) António J. A, Eliana S Solid lipid nanoparticle as a drug delivery system for peptide sand proteins. Advanced Drug Delivery Reviews 2007; 59:478–90.
3) Mishra S,Suryawanshi R,Chawla V,Saraf S. Fabrication and characterization of solid lipid microparticles of Ketoprofen. Ars Pharm 2011; 52:12-5.
4) Rosanna T, Geraldine P, Luc D, Santo Solid lipid microparticles containing the Sun screenmagent, octyl-dimethylaminobenzoate: Effect of the vehicle. Eur J Pharm Biopharm 2007; 66:483-7.
5) Santo S, Matteo M. Incorporation of quercetin in lipid microparticles: Effect on photo and chemical-stability of Pharm and Biomedical Analysis 2009; 48:90-4.
6) Giovannelli L, Bellomi S, Pattarino F, Albertini B. Characterization of Nifedipine microparticles prepared by Hot Air Coating technique. Int J Pharm 2005; 293:225-34.
7) MarjaS,Cynthia K , Hakan G, Carina D, Anne M J. Evaluation of controlled-release Polar lipid microparticles. Int J Pharm 2002; 244:151-61.
8) Yadav VR Suresh S, Devi K, Yadav S. Novel formulation. Of solid lipid microparticles of curcumin for anti-angiogenic and anti-inflammatory activity for optimization of therapy of inflammatory bowel disease 2009; 61:311-21.
9) Ruoxi W, Zhigang T, Lingyun C. Nano-encapsulations liberated from barley protein Microparticles for oral delivery of bioactive compounds. Int J Pharm 2011; 406:153-62.
10) Zhang N, Ping Q, Huang G, Xu W, Cheng Y, AHaHan X. Lectin-modified solid lipid nanoparticle as carriers for oral administration of insulin. Int J Pharm 2006; 327:153-159.
11) Nicoleta B, Christian AS, Michelangelo F, Olivier J, Eric D. Dexamethasone-containing PLGA superparamagnetic microparticles as carriers for the local treatment of arthritis. Biomater 2009; 30:1772-80.
12) Santoyo S, Gade Jalon E, Ygartua P, Renedo MJ, Blanco-Prieto MJ. Optimization of Topical cidofovir penetration using Microparticles. Int J Pharm 2002; 242:107-13.
13) Manmohan S, Jia H F, Jina K, Mildred U,James C, Padma M.A modified process for preparing cationic polyactide-co-glycolidemicroparticles with adsorbed DNA.IntJ Pharm 2006;327:1–5.
14) Hori M, Onishi H, Machida Y. Evaluation of Eudragit-coated microparticles as an oral immune delivery system. Int J Pharm 2005; 297:223-224.
9 / Signature of the Candidate /
(NIZAMUDDIN)
10 / Remarks of the Guide / The topic selected for dissertation is satisfactory.
11 /
Name and Designation
11.1 / Guide / MR.S.RAJARAJAN
ASSISTANT PROFESSOR
DEPT. OF PHARMACEUTICAL TECHNOLOGY
KARNATAKA COLLEGE OF PHARMACY#33/2, THIRUMENHALLIHEGDE NAGAR MAIN ROAD BENGALURU-64.
11.2 / Signature of Guide / (MR.S.RAJARAJAN)
11.3 / Co-Guide / NOT APPLICABLE
11.4 / Signature of Co- Guide / NOT APPLICABLE
11.5 / HOD OF PHARMACEUTICAL TECHNOLOGY / DR. B.PRAKASH RAO
KARNATAKA COLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BENGLURU-64.
11.6 / Signature of HOD / (DR.B.PRAKASH RAO)
12 / 12.1 / Remarks of the principal / All the required facilities will be provided to carry out dissertation work under the supervision of the guide.
12.2 / Principal / DR.K. RAMESH.
PRINCIPAL
KARNATAKA COLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BENGALURU-64.
12.3 / Signature of the Principal / (DR.K. RAMESH)