ISBN : 978-93-85073-24-3 Polymeric Nanocarriers for the Dr.Ram Prakash Aharwal, Department of chemistry, Dr. Hari Singh Gour University ( A Central University), Sagar. M.P. . : He did his post graduation and doctorate in chemistry from Dr. H. S. Gour Central University Sagar . Having more experience in the teaching, Crime investigation as scientific officer in Forensic Science Laboratory Sagar and Bhopal (M.P). He had attend many National and international conferences. He has published many National and international paper. He is also subject expert for board of studies of various universities in India and abroad. He is also working experience in Pharmaceutical industry. Dissolution of Anti-Depressants Drugs by using Kinetic Model Author Dr.T.Lalitha, Dr.R.Saravanakumar Ram Prakash Aharwal Sandeep Kumar Shukla Archna Pandey Published by International Society for Green, Sustainable Engineering and Management ISO 9001:2015 certified for Research, Development &Training An Autonomous Organization, Under Public Trust Act, Government of West Bengal, India Organizational Member Rs.250/Polymeric Nanocarriers for the Dissolution of Anti-Depressants Drugs by using Kinetic Model The Indian Science Congress Association Indian Statistical Institute Quality Council of India ISBN : 978-93-85073-24-3 2019
Polymeric Nanocarriers for the Dissolution of AntiDepressants Drugs by using Kinetic Model
FINANCIAL ENGINEERING AND COMPUTATION During the past decade many sophisticated mathematical and computational techniques have been developed for analyzing financial markets. Students and professionals intending to work in any area of finance must not only master advanced concepts and mathematical models but must also learn how to implement these models computationally. This comprehensive text combines a thorough treatment of the theory and mathematics behind financial engineering with an emphasis on computation, in keeping with the way financial engineering is practiced in today’s capital markets. Unlike most books on investments, financial engineering, or derivative securities, the book starts from basic ideas in finance and gradually builds up the theory. The advanced mathematical concepts needed in modern finance are explained at accessible levels. Thus it offers a thorough grounding in the subject for MBAs in finance, students of engineering and sciences who are pursuing a career in finance, researchers in computational finance, system analysts, and financial engineers. Building on the theory, the author presents algorithms for computational techniques in pricing, risk management, and portfolio management, together with analyses of their efficiency. Pricing financial and derivative securities is a central theme of the book. A broad range of instruments is treated: bonds, options, futures, forwards, interest rate derivatives, mortgage-backed securities, bonds with embedded options, and more. Each instrument is treated in a short, self-contained chapter for ready reference use.
Polymeric Nanocarriers for the Dissolution of AntiDepressants Drugs by using Kinetic Model By Ram Prakash Aharwal Sandeep Kumar Shukla Archna Pandey Published by International Society for Green, Sustainable Engineering and Management ISO 9001:2015 certified for Research, Development &Training An Autonomous Organization, Under Public Trust Act, Government of West Bengal, India Member The Indian Science Congress Association Quality Council of India Indian Statistical Institute 2019
© International Society for Green, Sustainable Engineering and Management Editor in Chief: Dr.Debaprayag Chaudhuri, Chairman Production Editor: Mrs.Sonali Chaudhuri Published in India by International Society for Green, Sustainable Engineering and Management 94,Garfa Main Road, Ground Floor, Jadavpur, Kolkata-700 075,West Bengal India Mobile:0091 96 74 76 61 80 Email: isgsem.research.kolkata@gmail.com Website: http://www.facebook.com/isgsem Copyright © 2019.All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical or photocopying, recording, or otherwise without the prior permission of the publisher. The society names used in this set are for identification purposes only. First Edition: December’2019 ISBN13 978-93-85073-24-3 (Print with paper binding) 250/
ISBN : 978-93-85073-24-3 Title: Polymeric Nanocarriers for the Dissolution of Anti-Depressants Drugs by using Kinetic Model Ram Prakash Aharwal*, Sandeep Kumar Shukla*, Archna Pandey* Department of Chemistry Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar (M.P) 470003 E-mail Id: rpaharwal9@gmail.com, prof.archnapandey@gmail.com In general, the development of drug nanocarriers for poorly soluble pharmaceuticals represents a special task and still faces some unresolved issues. The therapeutic application of hydrophobic, poorly water-soluble agents is associated with some serious problems, since low water-solubility results in poor absorption and low bioavailability [1]. In addition, drug aggregation upon intravenous administration of poorly soluble drugs might lead to such complications as embolism [2] and local toxicity [3]. On the other hand, the hydrophobicity and low solubility in water appear to be intrinsic properties of many drugs [4], since it helps a drug molecule to penetrate a cell membrane and reach important intracellular targets [5-6]. To overcome the poor solubility of certain drugs, clinically acceptable organic solvents are used in their formulations, as well as liposomes [7]. Another alternative is associated with the use of various micelle-forming surfactants in formulations of insoluble drugs. Delivering water-insoluble drugs, reducing severe systemic toxicities and increasing the utilization of drugs by improving their pharmacokinetics posed many challenges for drug delivery system (DDS) and drug development [8]. Recently, several type of drug carrier, such as microspheres, liposomes, nanoparticles [9] and polymeric carriers have been investigated as DDS, but non-selective scavenging of these carriers by the reticuloendothelial system (RES) is a serious problem. The structure of nanocarriers first developed in 1970 has since been optimized in order to improve their biodistribution. Polyethylene glycol (PEG) is grafted to nanoparticles and liposomes, increasing their stealth capacity and consequently, their systemic residence time in the blood-stream [10]. Nanocarriers injected by the systemic route and used for drug delivery have to respect some essential conditions [11]. 1
ISBN : 978-93-85073-24-3 As new polymers with innovative properties became available, selection of the right polymers for certain application became critically important. This led to strong demands on more efficient and more functional drug delivery vehicles. As polymers with new properties were developed, more needs were founds to develop polymers with even more intricate properties. It is most desirable if the polymers with advanced properties are synthesized with specific functions designed for drug delivery, such as drug solubilization and drug targeting, and for solving emerging problems. For this reason, it is beneficial to understand the current drug delivery technologies and the unique roles of polymers [12]. The various forms of natural and synthetic polymers are used for drug encapsulation and to deliver compound. The chitosan, a natural and antioxidative polymer obtained from crustacean shell [13] and the synthetic polymers L-D-, and D,L- polylactic acid (PLA), polyglycolic acid (PGA), and polycaprolactic acid (PCL), polyvinyl alcohol, polyethylene glycol (PEG), poly-Nvinylpyrrolidone, etc. have been used for controlled release of drug thereby reducing unwanted side effects and improving therapy [14-17]. The formulation of nano-sized particles can be implemented to all drug compounds belonging to biopharmaceutical classification system (BCS) classes II and IV to increase their solubility and hence partition into gastrointestinal barrier [18]. Micronization is used for class II drugs of (BCS), i.e. drugs having a good permeability and poor solubility [19-21]. There are many conventional methods for increasing the solubility of poorly soluble drugs, which include micronization [22], solubilisation using co-solvents [23], salt form [24], surfactant dispersions [25], precipitation technique [26-27] and oily solution. Other techniques are like liposomes [28], emulsions [29-30], microemulsion [31-32], solid dispersion [33-34], and inclusion complexation using cyclodextrins [35-37] show sensible achiever, but they lack in universal applicability to all drugs. These techniques are not applicable for those drugs which are not soluble in aqueous and organic solvents. Nanotechnology can be used to solve the problems associated with these conventional approaches for solubility and bioavailability enhancement. Nanotechnology is a multidisciplinary scientific field undergoing explosive development. One of the greatest values/promises of nanotechnology is in the development of new and effective medical treatments, such as nanomedicine [38-39]. The early concept of nanomedicine was inspired from the idea of fabrication of nano2
ISBN : 978-93-85073-24-3 sized robots that could be introduced into the human body and perform cellular repairs at the molecular level. However, the first scientist to voice the possibility of nanomedicine was the Noble physicist Richard P. Feymman, who in his historical 1959 lecture at Caltech said “There’s plenty of room at the bottom” and even proposed the first known nanomedical procedure to cure heart disease through “swallowing the surgeon” [40]. Based on Feymman’s insight into nanomedicine, manipulation of the materials/devices at the molecular level, nanomedicine today has evolved and branched into hundreds of different directions, e.g. nanoparticles, biosensors and nanotherapeutics [41]. Many approaches are being actively pursued towards nanomedicine. One of the nanomedical approache is to develop nanoparticles as carriers for drug molecules to achieve enhanced bioavailability, therefore, controlled drug delivery [42-44]. Bioavailability refers to the availability of the drug molecules at the specific site over a period of time. Tuning for enhanced bioavailability, which could not be achieved by the small-molecule drug alone, relies on manipulations of the nanocarriers. Nanoparticles (diameter < 1000 nm) are one attractive system as nanocarriers for controlled drug delivery, because they have the abilities to protect the therapeutics from degradation and help them to achieve improved solubility, increased loading capacity, and prolonged circulation time. In addition, they can also incorporate multiple types of therapeutics and various detection elements into one single formulation for imaging and more effective treatment. Furthermore, they can be functionalized with targeting ligands at the surface to obtain targeted delivery of therapeutics [45-54]. Therefore, lots of researchers are pursuing the nanoparticle approach for therapeutic delivery. The arsenal of nanoparticles at the forefront of the controlled drug delivery research includes dendrimers [55-57], polymer micelles [5860], chitosan nanoparticles [61-65], liposomes [66-70], polymersomes [71-76], carbon assemblies [77-79], gold nanoparticles including nanoshells and nanocages [80-84]. Need of Nanocarriers Nanotechnology is a novel area of science that provides, with a new hope, the tools and technology to work at atomic, molecular and supramolecular levels leading to creation of devices and delivery systems with fundamentally new properties and 3
ISBN : 978-93-85073-24-3 functions. A nanocarrier offers a number of advantages making it an ideal drug delivery vehicle (Fig 1.1). • Nanocarriers can better deliver drugs to tiny areas within the body [85]. • It represents engineering of particles, which are smaller than 100 nanometers. • Nanotechnology is so complementary to biotechnology that promises to bridge the gaps between ‘the structure’ and ‘the function’ of biomolecules as well as between ‘human physiology’ and ‘pathophysiology’. • This allows the engineering of products on a comparable scale to nature such as biologicals like proteins, DNA and viruses, which are of the order of 10’s of nanometers in size and cells and cellular assemblies of the order of 1000’s of nanometers. • It involves overlap of biotech, nanotech, and information technology, might result in many important applications in life sciences including areas of gene therapy, drug delivery, imaging, biomarkers, biosensors and novel drug discovery techniques [8688]. • It also offers an attractive solution for transformation of biosystems, and provides a broad platform in several areas of bioscience [89-90]. • Nanocarriers overcome the resistance offered by the physiological barriers in the body because efficient delivery of drug to various parts of the body is directly affected by particle size. • Nanocarriers aid in efficient drug delivery to improve aqueous solubility of poorly soluble drugs [91-92], that enhance bioavailability [93] for timed release of drug molecules, and precise drug targeting [94-95]. • The surface properties of nanocarriers can be modified for targeted drug delivery [96-97] e.g. small molecules, proteins, peptides, and nucleic acids loaded nanoparticles are not recognized by immune system and efficiently targeted to particular tissue types [98]. • Targeted nano drug carriers reduce drug toxicity and provide more efficient drug distribution [99]. 4
ISBN : 978-93-85073-24-3 • Nanocarriers holds promise to deliver biotech drugs over various anatomic extremities of body such as blood brain barrier, branching pathways of the pulmonary system and the tight epithelia junctions of the skin etc. • Nanocarriers better penetrate tumors due to their leaky constitution, containing pores ranging from 100-1000 nm in diameter. Fig 1.1: Multidisciplinary Functions of Nanocarriers Anti-Depressants Depression is estimated to affect nearly 340 million people worldwide and 18 million people in the United States at any given time [100]. A number of studies have documented the enormous impact of this debilitating condition on both patients and the health care system [101-104]. In the primary care setting, diagnosis of a depressive disorder is complicated by the fact that depressed patients frequently present with a combination of emotional and physical symptoms [105-109]. The importance of physical symptoms was highlighted by a recent international study which found that almost 70% of depressed patients reported physical symptoms as the only reason for visiting their physician [110]. Physical symptoms often associated with depression include headaches, back pain, gastrointestinal disturbance (e.g., irritable bowel syndrome), and generalized aches and pains [111]. 5
ISBN : 978-93-85073-24-3 Antidepressants are usually classified according to structure [e.g., tricyclic antidepressants (TCAs)] or function [e.g., monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs)]. However, it may be more useful to classify them according to the acute pharmacologic effects that are presumed to trigger behavioral improvement. If this is done, the antidepressants can be grouped in four categories (Table 1.1). First are the drugs that selectively block the reuptake of norepinephrine (NE). These include certain TCAs and TCA-like compounds (maprotiline). Another drug that falls into this category is reboxetine, although it is distinct structurally from the TCAs and TCA like compounds [112]. Second are the SSRIs, which, as their class name implies, selectively block the reuptake of serotonin [5-hydroxytryptimine (5-HT)] in-vivo. Third are the drugs that act nonselectively on noradrenergic and serotoninergic neurons with a resultant enhancement of synaptic transmission. Some TCAs are in this category, as are the MAOIs. Some novel drugs are also in this category [113]. Table 1.1: MECHANISM-BASED CLASSIFICATION FOR ANTIDEPRESSANTS Category Mechanism I Selective blockade of NE reuptake (SNRIs) II Selective blockade of 5- HT reuptake (SSRIs) Nonselective III enhancement of NE and 5-HT transmission Unknown potent IV stimulatory effects on NE or 5-HT Examples DMI, NT amoxapine, maprotiline reboxetine Citalopram, fluoxetine, paroxetine, sertraline IMI, AMI phenelzine, tranylcypromine venlafaxine, mirtazapine Trimipramine, bupropion, nefazodone, trazodone TCA Current Classification (If Any) TCAs , TCA-like SSRIs TCAs, MAOIs (sometimes with SSRIs) 6
ISBN : 978-93-85073-24-3 5-HT, 5-hydroxytryptamine (serotonin); AMI, amitriptyline; DMI, desipramine; IMI, imipramine; MAOI, monoamine oxidase inhibitor; NE, norepinephrine; NT, nortriptyline; SNRI, selective norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant. In the fourth and final heterogeneous group are drugs without known potent, acute pharmacologic effects that result in enhancement of noradrenergic or serotoninergic transmission. In other words, their mechanisms of action are unknown. Drugs in this category include the TCA trimipramine and also bupropion, nefazodone, and trazodone. It has been speculated that bupropion acts through dopaminergic mechanisms because it is the only antidepressant that more potently blocks the reuptake of dopamine than that of either NE or 5-HT [114]. The brain is one of the most important organs of the human body, if not the most, and its homeostasis is of primary importance. In fact, specific interfaces also referred to as barriers; tightly regulate the exchange between the peripheral blood circulation and the cerebrospinal fluid (CSF) circulatory system. These barriers are represented by the choroids plexus (CP) epithelium (blood-ventricular CSF), the arachnoid epithelium (blood-subarachnoid CSF), and the BBB (blood-brain barrier interstitial fluid) [115]. The blood-brain barrier (BBB) (Fig 1.2) is the bottleneck in brain drug development and is the single most important factor limiting the future growth of neurotherapeutics [116]. 7
ISBN : 978-93-85073-24-3 Fig 1.2: Whole body autoradiogram of an adult mouse sacrificed 30 min after intravenous injection of radiolabeled histamine, a small molecule that readily enters all organs of the body, except for the brain and spinal cord. The transport of small molecules across the BBB is the exception rather than the rule, and 98% of all small molecules do not cross the BBB [117]. Despite the large number of patients with disorders of the CNS and despite the fact that so few large or small molecule therapeutics cross the BBB, there are few pharmaceutical companies in the world today that have built a BBB drug targeting program. However, even if a pharmaceutical company decided to develop a BBB program, there would be few BBB-trained scientists to hire because less than 1% of U. S. academic neuroscience programs emphasize BBB transport biology. Because most drugs do not cross the BBB, and because the industry is not providing solutions to the BBB problem, it is not surprising that most disorders of the CNS could benefit from improved drug therapy (Fig 1.3). For a small molecule drug to cross the BBB in pharmacologically significant amounts, the molecule must have the dual molecular characteristics of a) molecular mass under a 400- to 500-Da threshold, and b) high lipid solubility. 8
ISBN : 978-93-85073-24-3 Fig 1.3: Comprehensive Medicinal Chemistry database shows that, of more than 7000 small-molecule drugs, only 5% treat the CNS, and these drugs only treat four disorders: depression, schizophrenia, chronic pain, and epilepsy. There are few effective small or large molecule drugs for the majority of CNS disorders, with the exception of Parkinson’s disease, e.g., L-DOPA, and multiple sclerosis, e.g., cytokines. Solubility and Dissolution The term ‘solubility’ is defined as maximum amount of solute that can be dissolved in a given amount of solvent. It can also be defined quantitatively as well as qualitatively. Quantitatively it is defined as the concentration of the solute in a saturated solution at a certain temperature. In qualitative terms, solubility may be defined as the spontaneous interaction of two or more substances to form a homogenous molecular dispersion. A saturated solution is one in which the solute is in equilibrium with the solvent [118-120]. The solubility behavior of drugs remains one of the most challenging aspects in formulation development. The events that occur following oral administration of a solid dosage form. It is a well formulated dosage form; the two critical rate determining steps in the absorption of orally administered drugs are [121]: 9
ISBN : 978-93-85073-24-3 1. Rate of dissolution 2. Rate of drug permeation through the biomembrane. To assist successful oral drug development, in vitro dissolution testing has emerged as a preferred method to evaluate development potential of new APIs and drug formulations are shown in Fig 1.4. Fig 1.4: Roles of in-vitro dissolution testing in pharmaceutical drug development The Nernst-Brunner and Levich modification of the Noyes-Whitney equation (eq.1) identified the important factors to the kinetics of in-vivo drug dissolution. These factors include drug diffusivity and solubility in the GI contents, the surface area of the solid wetted by the luminal fluids and the GI hydrodynamics [122]. ------------------ 1 Where dC/dt is the dissolution rate, A is the surface area available for dissolution, D is the diffusion coefficient of the drug, Cs is the saturation solubility of the drug in the dissolution medium, C is the concentration of drug in the medium at time (t) and h is the thickness of the diffusion boundary layer adjacent to the surface of dissolving drug. Several physicochemical and physiological aspects can have a great influence on the factors in eq. (1) and therefore on the dissolution rate, such as crystalline form, 10
ISBN : 978-93-85073-24-3 drug lipophilicity, particle size, viscosity of the medium, solubilization by native surfactants and co-ingested foodstuffs and pka in relation to the GI pH profile [123]. The mechanism and kinetics of drug release are dependent on the solubility of the active moiety and the swelling and erosion properties of the polymer, with water soluble drugs being released predominantly by diffusion with a limited contribution from matrix erosion and anomalous diffusion resulting from the relaxation of the macromolecular polymer chains [124]. The release of water soluble moieties will typically follow first order release kinetics. Water insoluble drugs are released predominantly through matrix erosion and therefore exhibit time independent or zeroorder release kinetics [125-130]. The Biopharmaceutics Classification System In the past decade, a greater understanding of the molecular transport in relation to physico-chemical properties especially solubility has led to the evolution of a biopharmaceutics classification system (BCS), which is becoming a road map governing future drug design, development and delivery. The BCS sets the criteria for allowing a drug substance, in an immediate release form to circumvent a bioequivalence study. It classifies the drugs into four major categories (Table 1.2) according to two main parameters; the solubility and permeability behaviours of each molecule [131-132]. Table 1.2: Biopharmaceutics Classification System (BCS) of drug molecules Biopharmaceutics Classification System I High solubility – High permeabilitya II Low solubility – High permeabilityb III High solubility – Low permeabilityc IV Low solubility – Low permeabilityd a. Exhibit dissolution rate-limited absorption (generally very well absorbed). b. Exhibit solubility rate-limited absorption. c. Exhibit permeability rate-limited absorption. d. Exhibit both, solubility and permeability rate-limited absorption with very poor oral bioavailability. 11
ISBN : 978-93-85073-24-3 According to the BCS, the dissolution rate is the limiting factor for the absorption of class II and IV drugs. Currently, 40% of the NCE fall in these two classes. Such molecules provide potential challenges to the formulation scientist. Their poor water solubility almost inevitably leads to low oral bioavailability from conventional dose forms. Poor aqueous solubility is an industry wide issue, especially for pharmaceutical scientists in drug discovery and drug development. A poorly water soluble drug is usually associated with poor absorption and bioavailability upon oral administration [133]. Although a certain degree of hydrophobicity is necessary for a drug molecule to cross the cell membrane easily [134], the overall rate of absorption is dictated by the time required for the dosage form to release its contents, and for the drug to dissolve in the GI fluid [135]. The water solubility of ‘poorly soluble’ drugs is usually less than 100 µg/mL [136]. A further parameter useful for identifying ‘poorly soluble’ drugs is the dose:solubility ratio of the drug. The dose:solubility ratio is defined as the volume of GI fluids necessary to dissolve the administered dose. When this volume exceeds the volume of fluids available, one may anticipate incomplete bioavailability from solid oral dosage forms. In fact, developing dissolution test methods for poorly water-soluble drug products has been an important task to formulation scientists. Problems encountered with poorly water-soluble drug product include a low extent of drug release and a slow release rate. General strategies to enhance their dissolution patterns rely upon either changing the dissolution medium pH, or adding solubilizers such as surfactants cyclodextrin derivatives into a dissolution medium [137-145]. Polymeric Surfactant Detergents belongs to a class of compounds called surfactants, which are surface active agents that reduce interfacial surface tension in mixture (i.e., oil and water) by adsorbing to interfaces [146]. The ability of a detergent to participate in a specific biological/biochemical function is related to its structure; the polar hydrophilic portion of the detergents molecule is referred to as the “hydrophilic head group” while the nonpolar hydrophobic, portion is referred to as the “tail”. Surfactants play a major role in the absorption of drugs in the body [147-148]. In the late 1960s, micelles drew much 12
ISBN : 978-93-85073-24-3 attention as drug carriers owing to their easily controlled properties and good pharmacological characteristics [149-150]. Fig 1.5: Schematic representation of the micellization process. Micelles are formed when amphiphiles are placed in water. They consist of an inner core of assembled hydrophobic segments capable of solubilizing lipophilic substances and outer hydrophilic corona serving as a stabilizing interface between the hydrophobic core and the external aqueous environment [151]. Fig 1.6: Schematic representation of the micelle formation 13
ISBN : 978-93-85073-24-3 Micellization is a critical phenomenon when considering detergent applications. Each detergents can be characterized by its critical micelle concentration (CMC); the concentration of detergents above which monomers self-assemble into non-covalent aggregates (called micelles) [152-153]. The CMC actually does not occur at a single concentration, but rather, over a narrow concentration range. When the total detergent concentration is below the CMC, detergent monomers are free in bulk solution. However, as more detergent is added above the CMC, all additional detergent monomers will go into micelles. It is important to note that when the total detergents concentration is greater than the CMC, there is a monomeric detergent concentration equal to the CMC and a micellar detergent concentration equal to: (total detergent concentration)-CMC. The CMC can be determined by a variety of methods including surface tension measurements and conductivity measurements [154-155]. Micelles made of nonionic surfactants are widely used as adjuvants and drug carrier system in many areas of pharmaceutical technology and controlled drug delivery [156-161]. Significance of works In the last decade, an emerging interest has been growing towards brain drug targeting where issues have been widely discussed [162-169]. The increasing awareness of the lack of rational and common efforts among different and complementary research areas has pointed out the need for a deeper understanding and a closer collaboration among diverse research experts of the field [170]. The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. For decades pharmaceutical sciences have been using nanoparticles to reduce toxicity and side effects of drugs. The book has explored the most recent intellectual property on polymer-based nanotechnological strategies for the design of optimal drug delivery devices. This is an effervescing area, with large investment volumes being poured by both public and private sectors. Most of the novelties still remain as experimental enterprises and are dealing with regulatory agencies to get approval. A key feature is to understand and internalize that due to the multidisciplinary nature of this area convergence of different professionals is demanded to bring a product to the market. In this book, we found that calculation and comparison of partial solubility parameters of polymer and drug could be used as a reliable means to predict which 14
ISBN : 978-93-85073-24-3 polymer is most suitable for development of a micelle based formulation for a specific drug. The ultimate goal of the test is to generate information that can provide an insight into the mechanism by which the drug is being released from the dosage form and provide data to facilitate the rational and rapid research, optimization and development of a modified release dosage form. The drug releases based on polymeric micelles that are currently in clinical trial evaluation represent significant milestones in this area. These advancements encourage further efforts in the design and development of polymer based nanocarriers as drug delivery vehicles. The interdisciplinary efforts in this field bringing together polymer chemist, pharmaceutical and medical scientists will continue to move the research forward to create new and improved technologies that are tailor made to suit the delivery of challenging molecules. It is only a matter of time before a formulation based on polymeric micelles is approved for treatment. The technological approach is a non-invasive method of drug delivery to the CNS. It is based on the use of nanosystems (colloidal carriers), which could be lipidbased (liposomes or solid lipid nanoparticles) or polymer-based nanoparticles. Nanotechnological approaches to neurodevelopmental, neurological and neuropsychiatric disorders include (a) using nanoparticles or nanocarriers to deliver drug or gene therapies, (b) using nanotechnology to reconstruct, reinforce, and/or stabilize the cytoskeletal matrix, (c) using nanofabrication methods to make biohybrid transport devices, and (d) coating electrodes with nanoparticles. Thus, this field of research represents one of the most stimulating challenges for the scientific world, as a result of the limited number of therapeutics capable of reaching the most ‘secret and sacred’ system of the body, the CNS. Nanotechnology is a multi disciplinary field, convergence of basic sciences and applied disciplines like biophysics, molecular biology, and bio engineering. Size reduction is a fundamental unit operation having important application in pharmacy. Major advantages of nano sizing include - (a) Increase surface (b) Enhanced solubility (c) Increase rate of dissolution and oral bio availability (d) Rapid onset of action (e) Less amount of dose required in the field of pharmacy. For applications to medicine and physiology these materials and devices can be designed to interact with a 15
ISBN : 978-93-85073-24-3 high degree of functional specificity, thus allowing a degree of interaction between technology and biological systems not previously attainable. It should be appreciated that nanotechnology is not in itself a single emerging scientific discipline but rather a meeting of traditional sciences such as chemistry, physics material science and biology to bring together the required collective expertise needed to develop these noval technologies. Numerous nanoparticle-based drug delivery and drug targeting systems are currently developed or under development. Their use aims to minimize drug degradation upon administration, prevent undersirable side effects, and increase drug bioavailability and the fraction of the drug accumulated in the pathological area. Author wish that pharmaceutical drug carriers, especially the ones for parenteral administration, are expected to be easy and reasonably cheap to prepare, biodegradable, have small particle size, possess high loading capacity, demonstrate prolonged circulation, and, ideally, specifically or non-specifically accumulate in required pathological sites in the body. In conclusion, even a brief listing of some key problems of nanocarriermediated drug delivery to brain shows how broad and intense this area is. In addition to this, nanoscale-based delivery strategies are beginning to make a significant impact on BBB- targeting programe and also global pharmaceutical planning and marketing. References 1. V. P. Torchilin, J. Control. Rel., 73, 137, 2001 2. A. M. Fernandez, K. Van Derpoorten, L. Dasnois, K. Lebtahi, V. Dubois, T. J. Lobl, S. Gangwar, C. Oliyai, E. R. Lewis, D. Shochat, A. Trouet, J. Med. Chem., 44, 3750, 2001. 16
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