RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA.
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1.0 / Name of the candidate and address / GNANESWARI KARRID no.41-2-168, Thadithota, Rajahmundry,
East Godavari (Dist),
Andhra Pradesh.
2.0 / Name of the Institution / R. R. college of pharmacy
Raja Reddy Layout,
Chikkabanavara post,
Hesaraghatta Main Road,
Bangalore-560 090.
3.0 / Course of the study and subject / M. Pharmacy
(Pharmaceutics)
4.0 / Date of admission / 8th November - 2010
5.0 / TITLE OF THE PROJECT
FORMULATION AND CHARACTERIZATION OF NANOPARTICLES OF A MODEL ANTI-HYPERTENSIVE DRUG
6.0
6.1 / BRIEF RESUME OF THE INTENDED WORK
Need for the study
Nanoparticles are transport carrier compartments for drugs or other active molecules of nano-liposomal character in the nanometer size range (10-1000nm). The advantages of nanoparticles as drug delivery systems are that they are biodegradable, nontoxic and capable of being stored for a period up to 1 year. Since they are taken up by the reticuloendothelial system following intravenous administration, nanoparticles are useful in delivering drugs to the liver and to cells that are active phagocytically. As such, nanoparticles can be used as lysosometric carriers. Furthermore, by modifying the surface characteristics of nanoparticles by coating them with substances such as surfactants, it is possible to enhance delivery of nanoparticles to the spleen relative to the liver.1
Nanoparticle formulations have many advantages over traditional dosage forms. Special pure drug nanoparticles offer some encouraging results for delivery drugs to various organs and through various routes. The colloidal carriers biodegradable and biocompatible polymeric systems have largely influenced the controlled and targeted drug delivery concept.2 Creating nano materials such as nano particles, nanotubes and thin films is the key component for a successful development of nanotechnology owing to their extraordinary physical and chemical properties resulting from the nano size effect.3
There is enormous excitement regarding nano medicinal potential impact in the diagnostic and therapy arenas. Specifically, drug delivery via nanoparticles presents novel therapeutic opportunities for active agents (drugs or genes) that are previously unsuited to traditional oral (or) injectable therapeutic formulations, allowing active agents to be delivered efficaciously while minimizing side effects and leading to better patient compliance. In theory nano technology should reduce the cost of drug discovery, design, and development. It should enhance the drug discovery process itself through miniaturization, automation, speed, massive, parallelism and reliability of assays.4
For a past few decades, there has been a considerable research interest in the area of drug particulate systems like nanoparticles have been used as a physical approach to alter and improve the pharmacokinetic and pharmacodynamics properties of various types of drug molecules.5 During last two decades, considerable attention has been given to the development of novel drug delivery system.6 A novel method applicable to synthesize water soluble drugs in the form of nano particles is reported. Since nanoparticles made of drugs below 100nm in size enhances the transport properties across biological cell membranes to reach a target site.7
A novel drug delivery systems an opportunity for formulation scientists to overcome the many challenges associated with Antihypertensive drug therapy, thereby improving the management of patients with hypertension. Currently available Antihypertensive drugs can be classified into these categories: ACE-inhibitors, angiotensin antagonist, calcium channel blocker, diuretics, central sympathomimetics alpha-adrenergic blocker, vasodilator, beta adrenergic blocker. Most of the drugs bear some significant draw backs such as relatively short half-life, low bioavailability poor permeability and undesirable effects. Efforts have been made to design drug delivery systems for Antihypertensive drugs to: a)Increase the bioavailability, b) Reduce the dosing frequency c)Deliver them to the target cells selectively with minimal side effects.8 The stability of this formulation is another attraction for the pharmaceutical scientists, while other novel drug delivery systems like liposomes, and niosomes suffer with stability problems, both in vitro and invivo.9
Methods of incorporating drugs in to nanoparticles are as follows:
· Colloidal coacervation of macromolecules.
· Adsorption on the surface of solid colloidal macromolecular carriers.
· Coating of the particles by polymerization, polycondensation, or coacervation.
· Interfacial polymerization technique using electrocapillary emulsification.1
· Ionic gelation method.10
· Nano precipitation method.6
· Modified solvent injection method.14
Hence present study is proposed to enhance bioavailability of drug and formulate it as a nanoparticle.
6.2
6.3 / REVIEW OF LITERATURE
1. Tamizhrasi. et al., formulated and evaluated of lamivudine loaded poly methacrylic acid nanoparticles. The aim of this study was to prepare and evaluate poly methacrylic acid nanoparticles containing lamivudine in different drug to polymer ratio by nano precipitation method. SEM indicated that nanoparticles have a discrete spherical structure without aggregation. The average particle size was found to be 121 + 8 - 403 + 4 nm. The particle size of the nanoparticles was gradually increased with increase in the proportion of poly methacrylic acid polymer. The in-vitro release behaviour from all the drug loaded batches was found to be zero order and provided sustained release over a period of 24 h. The developed formulation overcome and alleviates the drawbacks and limitations of lamivudine sustained release formulations and could possibility be advantageous in terms of increased bioavailability of lamivudine.6
2. ParthaSaha. et al., formulated and evaluated chitosan-based Ampicillin Tri hydrate nanoparticles. Ampicillin tri hydrate-loaded chitosan nanoparticles were prepared by ionic gelation method with the aid of sonication. Scanning electron microscopy revealed that the nanoparticles are in nano size range but irregular in shape. In vitro release data showed an initial burst followed by slow sustained drug release. The nanoparticles demonstrated superior anti -microbial activity to plain nanoparticles and the reference, due probably to the synergistic effect of chitosan and ampicillin tri hydrate. The chitosan nanoparticles developed would be capable of sustained delivery of ampicillin tri hydrrate.10
3. Selvakumar kalimuthu. et al., formulated and evaluated Carvedilol loaded Eudragit E 100 Nanoparticles. The aim of this work was to prepare Eudragit E 100 Nanoparticles of Carvedilol and to characterize them. Nanoparticles of Carvedilol with Eudragit E 100 were prepared by the Nanoprecipitation method using Polymeric stabilizer Poloxamer 407. The particles were characterized for particle size by photon correlation spectroscopy and transmission electron microscopy. The particle size of the prepared nanoparticles ranged from 190 nm – 270 nm. Nanoparicles of Carvedilol were obtained with high encapsulation efficiency (85-91%). These studies suggest that the feasibility of formulating carvedilol – loaded Eudragit E 100 nanoparticles for the treatment of hypertension.11
4. Adlin Jino Nesalin J. et al., formulated and evaluated Nanoparticles containing flutamide. In the present work nanoparticles of Flutamide were formulated using chitosan polymer by ionic gelation technique. Nanoparticles of different core: coat ratio were formulated and analyzed for total drug content, loading efficiency, particle size and in vitro drug release studies. From the drug release studies it was observed that nanoparticles prepared with chitosan in the core: coat ratio 1:4 gives better sustained release for about 12 hours as compared to other formulations.12
5. Umasankar. K et al., formulated and evaluated Nanoparticles of Cytarabine. The study deals with the formulation and evaluation of cytarabine nanoparticles. The purpose of this research is to minimize the frequency of doses and toxicity and to improve the therapeutic efficacy by formulating cytarabine nanoparticle. Cytarabine nanoparticles were formulating by ionic gelation method using polymer chitosan with three different ratios. Drug content was found to be supportive to the drug release pattern. The in vitro release of cytarabine nanoparticles were carried out which exhibited a sustained release of cytarabine from Nanoparticles upto 16 hours. The results showed that nanoparticles were more beneficial in providing drug delivery system.13
6. P.Khemaria. et al., formulated and evaluated solid lipid nanoparticles of Nateglinide. The purpose of present investigation was to formulative study for the development and in vitro evaluation of novel drug delivery carriers (i.e. Solid lipid nanoparticles) for Nateglinide. Method and characterization-Solid lipid nanoparticles (SLNPs) based on different lipidic components have been produced by modified solvent injection method and characterized for Nateglinide encapsulation efficiency, morphology, zeta potential, particle size, and drug release. Morphology and dimensional distribution have been investigated by electron microscopy and Photon Correlation Spectroscopy. Cell viability experiments demonstrate that SLNPs exhibit no toxicity. In vitro release kinetics based on a dialysis method demonstrated that Nateglinide was released in a prolonged fashion for 24 hours. These data suggest that SLNPs would be promising drug delivery carriers to enhance delivery of Nateglinide.14
7. M Sivabalan. et al., formulated and evaluated 5-Fluorouracil loaded Chitosan and Eudragit Nanoparticles for Cancer therapy. The goal of the investigation was to formulate and evaluate chitosan and Eudragit nanoparticles of 5- Fluorouracil for cancer therapy. Nanoparticles of 5- Fluorouracil were prepared using chitosan, Eudragit S 100, liquid paraffin and Tween -20 using Emulsion droplet coalescence method. The nanoparticles prepared were evaluated for morphology, loading efficiency, in vitro release and in vitro anticancer activities. The formulations CF1, CF2, EF2 and EF3 showed good drug release from the polymer. Among the four formulations EF 2 (1% Chitosan & 1.5 % Eudragit S 100) showed maximum drug release in 12 hours diffusion study and good entrapment efficiency. In-vitro anticancer study revealed that the formulated nanoparticles were found to have good cidal activity on cancer cells in sustained manner.15
8. Qiang Fu. et al., nanoparticle Albumin-Bound (NAB)Technology is a promising method for Anti-cancer Drug Delivery. The details about the preparation, characterization and evaluation of nab-paclitaxel (ABI-007) are discussed. The pharmacokinetics, pharmacodynamics and the clinical trials of ABI-007 are also reviewed. Furthermore, the recent applications of nab technology in the anti-cancer drug delivery systems are summarized by virtue of the patents pertaining to nab-technology. To sum up, nab-technology has a great potential of being applied extensively in the field of anti-cancer agents delivery in the future in order to acquire the good safety and better therapeutical effect.16
9. Hong-liang Zhang. et al., prepared and Characterised of Water soluble chitosan Nanoparticles as protein delivery system. The objective of this study was to investigate the potential of water soluble chitosan as a carrier in the preparation of protein loaded nanoparticles. Nanoparticles were prepared by ionotropic gelation of water soluble chitosan with sodium triphosphate. Bovine serum albumin (BSA) was applied as a model drug. The size and morphology of the nanoparticles were investigated. The result of the in vitro studies showed that the water soluble chitosan (WSC) nanoparticles enhance and prolong the intestinal absorption of BSA. The results also indicated that WSC nanoparticles were a potential protein delivery system.17
10. Avinash Budhian. et al., Controlling the in vitro release profiles for a system of haloperidol-loaded PLGA nanoparticles. They have used a systematic methodology to tailor the in vitro drug release profiles for a system of PLGA/PLA nanoparticles encapsulating a hydrophobic drug, haloperidol. They applied their previously developed sonication and homogenization methods to produce haloperidol-loaded PLGA/PLA nanoparticles with 200–1000 nm diameters and 0.2–2.5% drug content. The three important properties affecting release behaviour were identified as: polymer hydrophobicity, particle size and particle coating. Increasing the polymer hydrophobicity reduces the initial burst and extends the period of release. Increasing the particle size reduces the initial burst and increases the rate of release. It was also shown that coating the particles with chitosan significantly reduces the initial burst without affecting other parts of the release profile. Various combinations of the above three properties were used to achieve in vitro release of drug over a period of 8, 25 and >40 days, with initial burst <25% and a steady release rate over the entire period of release. Polymer molecular weight and particle drug content were inconsequential for drug release in this system.18
OBJECTIVE OF THE STUDY
Ø To develop the sustained release nanoparticle formulations of anti-hypertensive drug by using different polymers.
Ø To evaluate drug loaded nanoparticle formulations for physical and chemical properties.
Ø To carryout in vitro evaluation of nanoparticle formulations for the drug release characteristics.
Ø To enhance the bioavailability of anti-hypertensive drug.
Ø To reduce the undesirable effects of anti-hypertensive drug.
Ø To perform stability studies.
7.0
7.1 / MATERIALS AND METHODS
SOURCE OF DATA
Review of literatures from various sources such as;
,· International Journal of Innovative Pharmaceutical Research ,
· International Journal of Drug Development and Research,
· International Journal of Comprehensive Pharmacy,
· International Journal of Pharm Tech Research,
· International Journal of Pharmaceutical and Applied sciences,
· International Journal of Chem Tech Research,
· International Journal of pharmaceutics,
· International Journal of Research Pharmaceutical Sciences,
· Tropical Journal of Pharmaceutical Research,
· Bentham Science Publishers,
· Standard Books from our college library,
World wide web. www.wikipedia.com,
CD – ROM Search,
J-Gate@Helinet,
www.sciencedirect.com,
Laboratory based studies.
7.2 / METHOD OF COLLECTION OF DATA
Data on drug will be collected through survey from physicochemical database, handbooks, extensive pre formulation trial would provide the basis of selecting excipients and system for final formulation development. Experimental design assisted replicated experiment would be conducted to generate other data pertinent to formulation under investigation.
Formulation of sustained release nanoparticles of the anti-hypertensive drug by using different polymers.
Ø Particle size analysis.
Ø Surface morphology
Ø Zeta potential.
Ø Estimation of percentage yield and drug loading capacity of nanoparticles.
Ø To check drug polymer interaction and stability of drug by using Fourier Transform Infrared Spectroscopy (FTIR)
Ø Drug content
Ø In – Vitro drug release.
Ø Stability studies of nanoparticles
7.3 / Does the study require any investigation OR INVESTIGATION to be conducted on patient or other humans OR ANIMALS?
“No”
7.4 / Has ethical clearance been obtained from your institution in case of 7.3?
“NOT APPLICABLE”
8 / List of REFEReNCES1. Joseph R. Robinson., Vincent H. L. Lee. “Controlled Drug Delivery”, New York: Informa health care USA Inc., 2009, 462 pp.