Pharmaceutics & Novel Drug Delivery Systems

Formulation is defined as the method in which different chemical substances including the main active ingredient are compounded to produce a final dosage form. Developed formulations should be stable, safe and acceptable to the patient.

Global Contract Pharmaceutical manufacturing market is estimated to reach $94.63 billion by 2022 from $65.55 billion in 2016, at a CAGR of 6.31% for 2016 to 2022 period.  North America holds major share in Global Contract Pharmaceutical manufacturing market. Asia-Pacific especially India-is the fastest growing market. The main countries operating in this industry are US, Canada, China, India, Japan and Australia

The route of administration is the path through which the dosage form (active substance) is administered into the body for treatment of various diseases and disorders. Routes of administration are classified based on 1.the location at which the dosage form is applied 2. Target of action. These include oral, topical and enteral (system-wide effect, but delivered through the gastrointestinal tract), or parenteral (systemic action, but delivered by routes other than the GI tract).

Taking them correctly and understanding the right way to administer can reduce the risks. The route used to administer a drug depends on three main factors: 1. the part of the body being treated 2.the way the drug works within the body 3.the formula of the drug. These routes enhance the bio availability of drug molecule.

The global drug delivery technology market is projected to reach USD 1,669.40 Billion by 2021 from USD 1,179.20 Billion in 2016, at a CAGR of 7.2% during the forecast period. This market analysis is based on route of administration, facility of use.

The topical drug delivery market is expected to reach USD 125.88 Billion by 2021 from USD 92.40 Billion in 2016 at a CAGR of 6.4% from 2016 to 2021 forecast period.The oral drug delivery market was valued at $49 billion in 2010, and is forecast to grow at a CAGR of 10.3% until reaching $97 billion by 2017. 

Pharmacokinetics describes how the medicament gets influenced after administration, followed by absorption, distribution, metabolism mechanisms and excretion of the drug substance. Pharmacokinetic knowledge assist prescribers to adjust dosage more accurately and precisely. Clinical kinetics is defined as the applications of pharmacokinetic principles in the safe and adequate management of individual patient. Toxic pharmacokinetics is defined as the applications of pharmacokinetic principles to the design, behaviour and interpretation of drug safety evaluation studies.

Pharmacodynamics describes biochemical, physiological, and molecular effects of drugs on the body and involves receptor binding (including receptor sensitivity), post receptor effects, and chemical reactions. The pharmacologic response depends on the drug binding to its target. Pharmacodynamics is defined as the relationship between drug concentration at the site of action and the resulting effect. The effect of a drug present at the site of action is measured by drug-receptor binding.

Drug delivery devices are employed to inject drugs in the body through a particular route of administration, which in turn depends on the type of disease, desired action, and available   products.  These devices enhance the efficiency of the drug delivery system by controlling time, dosage, and site of release of the drugs in the body. Target specificity, dose-optimization and   high level of safety and efficiency are the characteristics of these devices. Devices may be conventional or implantable.

Rising geriatric population, technological advances, and increasing demand for improved drug delivery systems are the key tools driving the growth of the global drug delivery devices market.

The Global Drug Delivery Devices Market accounted to USD 1,027.0 billion in 2016 growing at a CAGR of 8.1% during the forecast period of 2017 to 2024.

Europe Drug Delivery Market expected to reach USD 536.1 billion by 2024 from USD 305.5 billion in 2016, at a CAGR of 7.3% in the forecast period 2017 to 2024.

Some of the major companies in Drug Delivery Devices market are 3M Company, Merck & Co., Inc., Pfizer Inc., Johnson & Johnson, Pfizer, Inc., Bayer AG, F. Hoffmann-La Roche AG, Abbott, Novartis AG, Valeant Pharmaceuticals International, Inc., Mylan Pharmaceuticals Inc., Antares Pharma.

Drug delivery is the action of administering a pharmaceutical drug into the body for a therapeutic effect through various routes. Drug delivery technologies modify drug release profiles, pharmacokinetic parameters for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. Conventional routes cannot deliver compounds such as proteins, antibodies, vaccine and gene based drugs because these routes are susceptible to enzymatic degradation or cannot be absorbed into the systemic circulation efficiently due to large molecular size and charge issues.

Technologies include digitally controlled needle-free devices, sustained and controlled transdermal delivery technology, fiber-based technology for implantable devices, targeted penetration matrix technology for non-invasive delivery and location-specific nano devices for chemotherapy delivery. Many innovative technologies for effective drug delivery have been developed, including implants, nanotechnology, cell and peptide encapsulation, micro fabrication, chemical modification.
Biotechnology advances are leading to develop medications that can target diseases more effectively and precisely. If a drug is more targeted, the chance of triggering drug resistance is lower, a cautionary concern surrounding the use of broad-spectrum antibiotics.

Nanotechnology delivers drugs to targeted cells using nanoparticles. The overall drug consumption and side-effects are lowered significantly by depositing the active drug in the particular site and preventing administration of booster doses. Nanotechnology based devices are less invasive, can be safely implanted inside the body and biochemical reaction times are much shorter. 

Nanotechnology became the driving force behind various evolutionary and revolutionary changes in the scientific field.  Nanotechnology drug delivery enhanced the efficacy of available medicaments and enabled to create entirely new medical products. Nanotechnology has opened the door to new approaches to stimulate the reconstruction of complex tissue structures. Nanoparticles are used to deliver the drug to the specific diseased cell where particles attract to the diseased cell and provide treatment. By this unique technique, we can minimize the damage of healthy cells in the body.

Nanotechnology-dependent detectors e.g. nanowires, nanotubes, nanoparticles, cantilevers, and nano arrays consume low sample and enhance fast detection of disease. Target based Nano probes (e.g. magnetic nanoparticles, quantum dots, and carbon nanotubes) provide a faster, less invasive, and more accurate way for early diagnose of diseases. Reporting in vivo efficacy of therapeutics and helping surgeons to locate tumors are other opportunities of nanotechnology.

Some nanotechnology-based drugs that are commercially available are- Abraxane, approved by the U.S. Food and Drug Administration (FDA) to treat breast cancer. Doxil was approved by the FDA for the treatment of ovarian cancer.

The global nanotechnology drug delivery market was valued at US$ 41,062.5 Mn in 2014 and is projected to reach US$ 118,527.2 Mn by 2023, expanding at a CAGR of 12.5% from 2015 to 2023.  

Key players having presence in the global nanotechnology drug delivery market are AbbVie, Inc., Amgen, Inc., Celgene Corporation, Johnson & Johnson, Merck & Co., Inc., and Novartis International AG, among others.

Targeted drug delivery is a kind of smart drug delivery, a method of delivering medication to a patient in a manner that increases the concentration only in particular part of the body. The goal of a targeted drug delivery system is to prolong, localize and have a protected drug interaction with the diseased tissue. The advantages of the targeted drug delivery are 1. reduction in the frequency of the dosages taken by the patient 2. have a more uniform effect of the drug, 3.reduction of drug side-effects 4. reduce fluctuation in circulating drug levels 5.maintain the required plasma and tissue drug levels in the body. In chemotherapy only a small portion of the medication reaches the affected organ and roughly 99% of the administered drug does not reach the tumor site.

While designing a targeted drug delivery, the following criteria must be taken into consideration: the drug properties, the route of drug delivery, the targeted site, disease and the side effects of drug. There are two kinds of targeted drug delivery: active targeted drug delivery, such as antibody medications, and passive targeted drug delivery, such as the enhanced permeability and retention effect.

A drug carrier improves the selectivity, effectiveness, and safety of drug administration. Drug carriers are primarily used to control the release of a drug into systemic circulation. This can be accomplished either by slow release of the drug over a long period of time (typically diffusion) or by triggered release at the drug's target by stimulus, such as changes in pH, application of heat, and activation by light. Drug carriers improve the bioavailability of poorly water soluble or membrane permeable drugs.

An ideal drug delivery vehicle must be non-toxic, biocompatible, non-immunogenic, biodegradable and must avoid recognition by the host's defense mechanisms. Different methods of drug attachment to the carrier include adsorption, integration into the bulk structure, encapsulation, and covalent bonding. As many drug delivery carriers are involved in delivery of the drug, the conference can be re-named as Drug Delivery carrier conference

One of the biggest challenges in the drug development for central nervous system (CNS) disorders is achieving significant blood–brain barrier (BBB) penetration.

Several drugs do not have high lipid solubility, low molecular size and positive charge to traverse BBB. The problems associated with the blood–brain barrier are1. The drug produced allows only a small amount to pass through the barrier 2. Binding to other proteins in the body renders the drug ineffective or pass through the barrier with the adhered protein. 3. The presence of enzymes in the brain that could render the drug inactive. All of these problems must be addressed and accounted to deliver effective drugs to the brain.

Nano biotechnology-based delivery methods provide the best approach to deliver drugs. Several developed strategies, enhance the capacity of drug molecules to cross the BBB by modifying the drug or by coupling it to a vector for receptor-mediated or adsorption-mediated transcytosis.

By 2019, compounds using BBB technology in the clinical development would reach approximately eight. The global market for BBB technologies was valued at $38.7 million in 2014. The market is expected to grow to $471.5 million by 2019, and register a tremendous 64.9% CAGR from 2014 through 2019.

Peptides and proteins have great potential as drug delivery. Compared with the small size drugs, peptides and proteins can be highly selective as they have multiple points of contact with their target. Increased selectivity also result in decreased side effects and toxicity. Peptides can be designed to target a broad range of molecules and provide opportunities in oncology, immunology, infectious disease and endocrinology. The market for peptide and protein drugs is estimated to be greater than US$40 billion/year, or 10% of the pharmaceutical market .At present there are over 100 approved peptide-based drugs in the market. The pharmaceutical scientists have approaches to develop the protein and peptide delivery formulations by noninvasive routes.

Gene therapy is defined as incorporation of genetic material i.e, DNA or RNA, in the cellular gene regulation system, either to correct the expression of a malfunctioning gene or to modulate the cellular functions. Nanotechnology advancements have given rise to the development of nanoparticle-DNA delivery systems. Gene delivery is an integral part of genome evolution. Gene delivery utilizes non-immunogenic vectors capable of cell specificity that can deliver an adequate amount of transgene expression to cause the desired effect. Advances in gene therapy have enabled a variety of new methods and gene targets to be identified for possible applications. Gene delivery has been utilized to generate a hybrid biosynthetic vector to deliver a possible vaccine.

Vaccine is a material that induces an immunologically mediated resistance to a disease but not necessarily an infection. Vaccines are generally composed of killed or attenuated organisms or subunits of organisms or DNA encoding antigenic proteins of pathogens. Vaccines though exceptionally selective and specific in reacting with antibodies often fail to show reactions in circumstances such as shifts in epitopic identification center of antibody and are poorly immunogenic. These vaccines require boosting with agents called adjuvants in order to induce an effective immunity. Adjuvants potentiate the immunostimulatory property of the antigen and are non-immunogenic, nontoxic, and biodegradable in nature.

Conventional immunization regimen involves prime doses and booster doses. Immunization failed as patients neglect the booster doses. These reasons necessitated the development of new generation of prophylactic and therapeutic vaccines to promote effective immunization. Vaccines allow for the incorporation of doses of antigens so that booster doses are no longer necessary as antigens are released slowly in a controlled manner. Attempts are being made to deliver vaccines through carriers as they control the spatial and temporal presentation of antigens to immune system thus leading to their sustained release and accurate targeting. Carrier systems such as liposomes, microspheres, nanoparticles, dendrimers, micellar systems, ISCOMs, plant-derived viruses are being investigated and developed as vaccine delivery systems

Materials are called “smart” when these materials have the ability to respond to stimuli and have high potential in novel drug delivery systems. The delivery of drugs to specific locations in the human body using smart materials has been approaching the forefront place in research for the past few decades. Materials for delivering drugs must design drug carriers that do not interact non-specifically within the body.

Polymers have played an important role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods and release of both hydrophilic and hydrophobic drugs. The greatest advantage of polymers  is their ability to chemical modification, resulting in defined chemical composition, customized surface functionality and the potential for defined three-dimensional structures. Several polymers widely used in clinical therapies are synthetic polymers and natural polymers.

Nano materials are used in controlled drug delivery. Drug-delivery systems can be synthesized with controlled composition, shape, size and morphology. Nanoparticles surface properties can be manipulated to increase solubility, immunocompatibility and cellular uptake.

Natural gums are one of the major areas for applications in the drug delivery system because of their wide availability, inexpensiveness.

Nanoparticles are generally less than 100 nm in dimension and consist of different biodegradable materials such as natural or synthetic polymers, lipids, or metals. Nanoparticles are taken up by cells more efficiently than larger micromolecules. Nanoparticles have high surface area to volume ratio thus allowing many functional groups for attachement. Additionally, the small size of nanoparticles allows them to accumulate at tumor sites.      

Nano particles can (1) enhance the therapeutic efficacy and minimize adverse reactions associated with available drugs; (2) enable new classes of therapeutics; and (3) encourage the re-investigation of pharmaceutically suboptimal but biologically active new molecular entities that were previously considered undevelopable.

Nanoparticles are used in targeted drug delivery to improve the uptake of poorly soluble drugs. Nano particles with different compositions and biological properties have been extensively investigated for drug and gene delivery application.

According to BCC Research the global market for nanoparticles in the life science forecast to grow to more than $79.8 billion by 2019, to register a healthy compound annual growth rate (CAGR) of 22%. 

The global nanotechnology market in environmental applications reached $23.4 billion in 2014. This market is expected to reach about $41.8 billion by 2020, registering a compound annual growth rate (CAGR) of 10.2% from 2015 to 2020.

The global market for nanotechnology products was valued at $22.9 billion in 2013 and increased to about $26 billion in 2014. This market is expected to reach about $64.2 billion by 2019, a compound annual growth rate (CAGR) of 19.8% from 2014 to 2019.

Novel drug delivery system addresses the limitations of the traditional drug delivery systems. We have a vast knowledge of Ayurveda and the drug delivery system used for administering the herbal medicine to the patient is traditional. So it is important to integrate novel drug delivery system and Indian Ayurvedic medicines to combat serious diseases.

Reasons for using herbal medicines are 1.  Growing concern over the reliance and safety of drugs 2.Failure of modern medicine to treat most common health conditions   3. Natural medicines are producing better results without side effects.

Novel herbal formulations like polymeric herbal Nano-carriers, phytosomes, herbosomes, pro-niosomes, Nano emulsions, microsphere, transferosomes, implants and ethosomes has been reported using bioactive plant extracts. Advantages include Solubility, bioavailability enhancements, reduced toxicity, improved pharmacological activity, sustained delivery, and protection from physical and chemical degradation. Many formulations are produced from various herbal drugs such as curcumin, quercetin, silybin, bilobalide, marsupsin, andrographolide.

According to WHO because of poverty and lack of access to modern medicine as well as self-belief, about 65-80% of the world's population living in developing and developed countries depends on plants for primary health.

In spite of discovery of various drugs, several challenges are unmet and there is always a need to compensate our resources in fighting to solve issues at a basic science level and also for the development of new drugs, new approaches for treatment. There is always a quest for new knowledge that is available today for any specific medical condition. There are several unknown solutions thus finding a novel drug for a disease is always a challenge. Following the path from discovery of a molecule through the road of development is complex and involves time, money and multiple disciplines to move it ahead.

Despite efforts to hasten the process of drug development using innovative technologies, the current efforts still appear to be ineffective. Several novel strategies like academia-industry interactions that foster a conversion of novel technologies to product and public – private funding have not helped to conquer several diseases Therefore, it becomes important to identify the areas in the development chain that needs to be improved by which one can hasten the process.

Pharmaceutical industry and drug discovery research applied all the basic scientific data and have developed procedures and guidelines that enable the conversion of information into useful tools that can be used to treat disease. But the curve of submissions of new drugs and biologics to FDA is in the opposite direction, a mirror image of the investment curve. The major concern is related mainly to the costs of preclinical and clinical trials studies. Reasons for submission curve are the industry's lower revenue growth, poor stock performance, the lowest number of new chemical entity (NCE) approvals and the poor late-stage R&D which  is  prevalent throughout the industry.

Innovative, non-invasive delivery include drivers like improvement of patient acceptability and compliance ,improvement in public safety, decrease of administration costs and a reduction of adverse effects. Enzyme degradation, acid degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract surfaces make oral administration a non-viable delivery method. Conventionally, many drugs such as proteins are administered parenterally since oral administration cause low bioavailability in the GI tract. It has become a challenge to achieve consistent and adequate bioavailability levels for oral administration.

Economic and financial barriers also stand in the way of implementing nano medicine. The limited availability of reimbursement by public and private health insurers for expensive new diagnostic tests has emerged as a major impediment to the deployment of personalized medicine. Nanoproducts encounter even greater hurdles because of their costs and complexity,  cytotoxicity of nanoparticles are  main concern of future research.

Advances in medical science, research and development (R&D) are changing the dynamics of the life science industry, including pharmaceuticals and healthcare. The development of new drugs necessitates the development of different drug delivery systems, which is further driven by innovation in technology, R&D and scientific advancements. Advances in understanding human biology, diseases and medical treatments are opening new opportunities in the pharmaceutical industry. A drug delivery system is an important area where the need for better technologies for drug administration or delivery is in demand

Activities have been increased regarding the development and research on various printing techniques in fabrication of dosage forms. These technologies offer flexibility in manufacturing, potentially pave the way for personalized dosing and tailor-made dosage forms.

Drug delivery from 3-dimensional (3D) structures is a rapidly growing area of research. 3DP can fabricate solid dosage forms with variable densities and diffusivities, complex internal geometries, multiple drugs and excipients.

3DP uses computer aided technology and programme to transform 3D computer aided designs (CAD) into life-changing products. These design more effective and patient-friendly pharmaceutical products as well as bio-inspired medical devices. Levetiracetam (SPRITAM^®) tablet a pharmaceutical product is developed by using 3DP technology.

3DP offers advantages like (a) high production rates due to its fast operating systems, (b) ability to achieve high drug-loading with much desired precision and accuracy especially for potent drugs that are applied in small doses, (c) reduction of material wastage which can save in the cost of production and (d) amenability to broad types of pharmaceutical active ingredients including poorly water-soluble, peptides and proteins, as well as drug with narrow therapeutic windows.

The pharmaceutical market in Russia is one of the fastest growing market globally and is set to rise from $20.91 billion in 2016 to $38.56 billion by 2021, representing a compound annual growth rate of 13%, according to GlobalData, Thus, Russia’s pharmaceutical market will almost double to $39billion by 2021.

The medical device market in Russia was valued at $6.7 billion in 2016 and is forecast to reach $8.5 billion in 2021. Major segments likely to experience high growth are ophthalmic devices cardiovascular devices, orthopedic devices.

Drug delivery technology market is projected to reach USD 1,669.40 Billion by 2021 from USD 1,179.20 Billion in 2016, at a CAGR of 7.2% during the forecast period.

Prominent players in this market include Johnson & Johnson, Inc., F. Hoffman-La Roche, Merck & Co, Inc. Bayer AG, Pfizer, Inc., Novartis AG, 3M Company, Becton, Dickinson and Company, GlaxoSmithKline plc. Sanoff  and Antares Pharma, Inc.

The Global Drug Delivery Technologies Market is poised to grow at a CAGR of around 7.9% over the next decade to reach approximately $2,222 billion by 2025.

North America dominates the global market for injectable drug delivery due to a large aging population and increasing incidences of diabetes. Asia is expected to witness high growth rates in the next five years in the global injectable drug delivery market. China and India are expected to be the fastest-growing injectable drug delivery markets in Asia Pacific. 

 The global transdermal drug delivery market was valued at $13.5 billion in 2013 and is expected to reach $21.7 billion by 2018, at a CAGR of 11.1% from 2013 to 2018.

An overview of the current global market for drug delivery and formulation enabled and enhanced products provides a sense of what is out there and what we might expect. Drug-Device enhancements over the past few years have generally been incremental and largely predictable in terms of features and performance.

The goal of drug delivery systems is to deliver medications to specific target parts of the body through a medium that can control the therapy’s administration. To achieve this goal, researchers are turning to advances in the worlds of micro- and nanotechnology.

The recent advances in the peptide and protein drug delivery systems are PEGylation and Depo-foam technology. Cell-penetrating peptides (CPPs) act as cargo carriers and constitute a current hotspot in medical research. CPPs to transport hydrophilic macromolecules into cells, thus, assist to execute biological functions. CPPs do not destroy the integrity of the cell membranes, and are considered more efficient and safe and providing new avenues for research and applications in life sciences.

Biologics can be re-engineered for BBB transport with the use of molecular Trojan horse technology. 

Needle-free drug delivery systems are novel ways to introduce various medicines to patients. PowderJect Pharmaceuticals one of the first companies to develop a needle-free technology for injecting powdered drugs into the skin. Needle free devices can take the form of power sprays, edible products, inhalers, and skin patches

Organizations such as W.H.O. and C.D.C. (center for disease control) support the development of needle free insulin drug delivery.

Transdermal patches are user-friendly, convenient, painless and offer improved patient compliance.

Nano drug delivery systems such dendrimers, fullerence, nano pores, nanotubes, nano shells, quantum dots, , nanovaccines, revolutionized drug delivery systems. Thus nanomaterial can be used for strategic development of new drug delivery systems and reformulate existing.

 Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterial have been shown to cross the blood-brain barrier.