Impact of Pharmacotherapy on Drug Delivery Systems

Introduction

Pharmacotherapy can be defined as the treatment and prevention of illness and disease by means of drugs of chemical or biological origin. It ranks among the most important methods of medical treatment, together with surgery, physical treatment, radiation and psychotherapy. Although it is almost impossible to estimate the exact extent of the impact of pharmacotherapy on human health, there can be no doubt that pharmacotherapy, together with improved sanitation, better diet and better housing, has improved people’s health, life expectancy and quality of life.

Unprecedented developments in genomics and molecular biology today offer a plethora of new drug targets. The use of modern chemical synthetic methods (such as combinatorial chemistry) enables the synthesis of a large number of new drug candidates in shorter times than ever before. At the same time, a better understanding of the immune system and rapid progress in molecular biology, cell biology and microbiology allow the development of modern vaccines against old and new challenges.

However, for all these exciting new drug and vaccine candidates, it is necessary to develop suitable dosage forms or drug delivery systems to allow the effective, safe and reliable application of these bioactive compounds to the patient. It is important to realize that the active ingredient is just one part of the medicine administered to the patient and it is the formulation of the drug into a dosage form or drug delivery system that translates drug discovery and pharmacological research into clinical practice.

Indeed the drug delivery system employed plays a vital role in controlling the pharmacological effect of the drug as it can influence the pharmacokinetic profile of the drug, the rate of drug release, the site and duration of drug action and subsequently the side-effect profile. An optimal drug delivery system ensures that the active drug is available at the site of action for the correct time and duration.

Drug delivery systems

Drug delivery refers to approaches, formulations, technologies, and systems for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effect.

· Drug delivery systems according to the physical state

Based on physical state, drug delivery systems may be:

– Gaseous (e.g. anaesthetics),

– Liquid (e.g. solutions, emulsions, suspensions),

– Semisolid (e.g. creams, ointments, gels and pastes) and

– Solid dosage forms (e.g. powders, granules, tablets and capsules).

· Drug delivery systems according to route of administration

Another way of differentiating dosage forms is according to their site or route of administration.

Parenteral drug delivery: Drugs can be administered directly into the body, through injection or infusion. Depending on the site of administration into the body it can be differentiated into:

a) Subcutaneous injection

b) Intramuscular injection

c) Intravenous injection

d) Intradermal injection

e) Intraperitoneal injection

Oral drug delivery: The oral route is the most popular route to administer drugs. Suspensions, tablets, capsules,etc are administered through this route.

– Topical drug delivery: Drugs can also be administered on to the skin to enter into the body. Mostly semisolid dosage forms are used for this, including creams, ointments, gels and pastes. However, liquid dosage forms, such as emulsions, or solid dosage forms, such as transdermal controlled drug delivery systems (patches), can also be used.

– Transmucosal: In this drugs are administered hrough nasal, buccal/sublingual, vaginal, ocular and rectal routes.

· Drug delivery systems according to mechanism of drug release

Another system that can be used to differentiate drug delivery systems is according to the way the drug is released. It can be differentiated as:

– Immediate release – drug is released immediately after administration.

– Modified release – drug release only occurs sometime after the administration or for a prolonged period of time or to a specific target in the body. Modified-release systems can be further classified as:

a) Delayed release: drug is released only at some point after the initial administration.

b) Extended release: prolongs the release to reduce dosing frequency

– Sustained release: These systems maintain the rate of drug release over a sustained period of time.

– Controlled release: Controlled-release systems also offer a sustained-release profile but, in contrast to sustained-release forms, controlled-release systems are designed to lead to predictably constant plasma concentrations, independently of the biological environment of the application site. This means that they are actually controlling the drug concentration in the body, not just the release of the drug from the dosage form, as is the case in a sustained-release system.

– Targeted drug delivery (smart drug delivery): It is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue.

Disease and Design of drug delivery system

A disease is an abnormal condition that affects the body of an organism. It is often construed as a medical condition associated with specific symptoms and signs. It may be caused by factors originally from an external source, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune diseases, it sometimes includes injuries, disabilities, disorders, syndromes, infections, isolated symptoms, deviant behaviors, and a typical variations of structure and function.

Medical therapies are efforts to cure or improve a disease or other health problem. A number of drug molecules have already been developed but development of further more new drug molecule is expensive and time consuming. So, improving efficacy ratio of “old” drugs is considered a good idea. This has been attempted by developing new drug delivery systems that helps in individualizing drug therapy, dose titration, and therapeutic drug monitoring easily. Delivering drug at controlled rate, slow delivery, targeted delivery are very attractive methods and have been pursued vigorously. Drug delivery systems modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety. It also ensures patient convenience and compliance.

There are some drug molecules which show site specific drug release eg, peptides and proteins. Such drugs cannot show their action without appropriate drug delivery system. So,the increasing number of peptide and protein drugs being investigated demands the development of dosage forms which exhibit site-specific release. Delivery of drugs into systemic circulation through colonic absorption represents a novel mode of introducing peptide and protein drug molecules and drugs that are poorly absorbed from the upper gastrointestinal (GI) tract. Oral colon-specific drug delivery systems offer obvious advantages over parenteral administration. Colon targeting is naturally of value for the topical treatment of diseases of the colon such as Crohn’s disease, ulcerative colitis and colorectal cancer. Sustained colonic release of drugs can be useful in the treatment of nocturnal asthma, angina and arthritis. Peptides, proteins, oligonucleotides and vaccines are the potential candidates of interest for colon-specific drug delivery. Sulfasalazine, ipsalazide and olsalazine have been developed as colon-specific delivery systems for the treatment of inflammatory bowel disease (IBD).

Worldwide, over 40 million people are infected with the Human Immunodeficiency Virus (HIV). The High Activity Antiretroviral Therapy (HAART) combines at least three antiretroviral (ARV) drugs and, for over a decade, has been used to extend the lifespan of the HIV-infected patients. Chronic intake of HAART is mandatory to control HIV infection. The frequent administration of several drugs in relatively high doses is a main cause of patient incompliance and a hurdle toward the fulfillment of the pharmacotherapy. High adherence to HAART does not lead to complete HIV virus elimination from the host. Intracellular and anatomical viral reservoirs are responsible for the perpetuation of the infection. Active transport mechanisms involving proteins of the ATP-binding cassette superfamily prevent the penetration of ARV drugs into the brain and may account for the limited bioavailability after oral administration. A new research that addresses from simple organoleptic or technological problems to more complex issues involving the targeting of specific tissues and organs has emerged. With the aim to reduce dosing frequency, to improve the compliance of the existing pharmacotherapy and to target viral reservoirs, the design of drug delivery systems is becoming complementary to new drug discovery.

Conclusion

Whenever a person suffers from a disease, he/she requires a medical treatment and every one of us prefer the safe, effective, economic and a convenient one. This can only be achieved by development of appropriate drug delivery system. No matter how dosage forms are classified, the role of the drug delivery systems is to allow the effective, safe, and reliable application of the drug to the patient.

For the proper Pharmacotherapy, delivery systems should allow and facilitate the drug to reach its target site in the body. For example, a tablet formulation containing an antihypertensive drug must disintegrate in the gastrointestinal tract, the drug needs to dissolve and the dissolved drug needs to permeate across the mucosal membrane of the gastrointestinal tract into the body. So, for the development of dosage forms the formulation scientist needs to optimize the bioavailability of the drug.

Similarly, the delivery system is to allow the safe application of the drug. This includes that the drug in the formulation must be chemically, physically and microbiologically stable. Side-effects of the drug and drug interactions should be avoided or minimized by the use of suitable drug delivery systems. The delivery systems also need to improve the patient’s compliance with the pharmacotherapy by the development of convenient applications. For example, one can improve patient compliance by developing an oral dosage form where previously only parenteral application was possible.

Finally, the delivery system needs to be reliable and its formulation needs to be technically feasible. However, for any application of a drug delivery system on the market, the dosage form needs to be produced in large quantities and at low costs to make affordable medicines available. Therefore, it is also necessary to investigate the feasibility of the developed systems to be scaled up from the laboratory to the production scale.

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