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.

Costly Tradeoff With the Wait for the Vaccine Pandemic Strategy

Americans and most of the global population for over a year have been consumed with fear, sacrifices and concerns about the COVID-19 pandemic. But few people have understood or been given a chance to support or reject what is best seen as the wait for the vaccine pandemic strategy.

Hidden from public view was a most substantial tradeoff between doing what was feasible to save lives of most people infected by COVID starting in the early months of the pandemic versus placing priority on waiting for COVID vaccines to be the pandemic salvation. This tradeoff violated key principles and ethics of medicine, and also undermined American democracy. Many nations followed what the US did.

Here is the most important aspect of this strategy. This tradeoff happened despite an enormous amount of data from the US and other nations that pioneering clinicians had found successful early home/outpatient COVID treatments. These were true cures, because they stopped the viral infection in its first viral replication stage. The treatment kept patients with symptoms out of the hospital.

So, another aspect of the tradeoff was that by not supporting early home/outpatient treatment hospitals became crushed by COVID victims that had passed through the first stage into greatly worse symptoms in the second and third stages of the infection. Enormous pain, suffering, deaths and costs were the inevitable consequence of not pushing early home/outpatient treatment and, instead, waiting for COVID vaccines.

Details and data on the considerable positive data on these treatments have been given in my book Pandemic Blunder. A pro-treatment article noted that two leading physicians used ivermectin to treat themselves when they got infected with COVID. One good source of data on early treatment should be promoted for public use.

Despite what many physicians and medical researchers concluded were treatments that cured COVID, others even today have negative views about the two most cheap generic medicines used in many treatment protocols and cocktails, namely hydroxychloroquine and ivermectin.

Data on the treatment success first started to be made public in March 2020, mostly by Dr, V. Zelenko, a frontline community physician in New York. A number of other clinicians followed through the early months of the pandemic and, even today, keep using both generics with remarkable success. But the mainstream and corporate social media have stubbornly refused to view the treatment “solution” in a positive way. The biggest reason for this refusal to truly follow the science is that under the leadership of Dr. Fauci both NIH and FDA issued guidance blocking wide use of both generics. These actions essentially killed wide use of COVID treatment for the general public as well as health care workers. What happened instead?

Behind the scene the leading federal officials at NIH, FDA and CDC decided to execute the wait for vaccine strategy and successfully convinced President Trump and his White House pandemic task force to pump billions of dollars into Operation Warp Speed in April 2020.

Dr. Peter McCullough made this important point: “All efforts on treatment were dropped. Warp Speed went full tilt for vaccine development, and there was a silencing of any information on treatment.” He has said that 85 percent of COVID deaths can be prevented with treatment. Back in November 2020 he said “we can prevent hospitalization and death,” and spoke of a crime against humanity because of negative views on early home treatment.

What is critically important to recognize is that out of the current 600,000 COVID deaths in the US over 500,000 could have been prevented with the treatment approach. Globally over 3 million lives could have been saved. This view of preventable deaths was an important conclusion in Pandemic Blunder based on clinical evidence.

Here too, big media has refused to acknowledge what so many experts have said about the enormous missed opportunity to save lives.

In my opinion, any physician who also has a negative view of the treatments based on hydroxychloroquine or ivermectin has either not spent sufficient time examining available data or has fallen victim to the propaganda and disinformation unleashed by big media. The record is clear. Both generics have many decades of safe use and are fully FDA approved. The websites of three organizations should be used by physicians to access good information on early treatments: Front Line COVID-19 Critical Care Alliance. America’s Frontline Doctors and the Association of American Physicians and Surgeons. People can get hydroxychloroquine or ivermectin through these groups.

Now we are in the COVID vaccine stage with all vaccines being used correctly categorized as experimental. They are not fully FDA approved but are used under an emergency use designation. Every day in the US and many other countries there is an endless flow of accounts of vaccine related deaths and serious negative health impacts. Two websites are good sources of information on vaccine related impacts: Health Impact News and The COVID Blog that are largely ignored by big media.

Dr. Peter McCullough has recently said that “if this were any other vaccine it would have been pulled from the market by now for safety reasons.” “Based on the safety data now, I can no longer recommend it. There are over 4,000 dead Americans, there are over 10,000 in Europe that die on days one, two and three after the vaccine,” said McCullough.

This is the reality for the COVID vaccines: As of May 7, there have been 192,954 adverse-event reports associated with COVID vaccines reported to the CDC’s Vaccine Adverse Event Reporting System [VAERS], including 4,057 deaths. Previous studies, including one from Harvard University, estimate that only 1 to 10 percent of all vaccine-related ill effects get reported to VAERS. In other words, there are probably more people dying from the COVID vaccines than has been reported. Importantly, as to informed consent, people receiving the vaccine are not told about the CDC data, nor are they knowledgeable about serious health impacts globally.

For comparison: There are 20 to 30 deaths reported every year to VAERS related to the flu shot. That’s with 195 million receiving flu shots, far more than COVID fully vaccinated people to this point.

Dr. Marty Makary, a truth-telling Johns Hopkins physician, has made the point that “natural immunity works” and it is wrong to vilify those who don’t want the vaccine because they have already recovered from the virus. “There is more data on natural immunity than there is on vaccinated immunity, because natural immunity has been around longer,” he emphasized. “We’ve got to start respecting people who choose not to get the vaccine instead of demonizing them,” Makary said. Recently has said that about 150 million Americans have natural immunity.

In the Fauci wait for the vaccine strategy, access to generics like hydroxychloroquine and ivermectin had to be choked. The federal stockpile of hydroxychloroquine was not used. The pandemic had to boil and create consumer demand for vaccines, even as enormous numbers of people worldwide died unnecessarily. Fauci and other federal doctors failed their oath to first do no harm, meaning their responsibility to act quickly to treat their patients and avoid hospitalization and possible death.

6 Tips for Packing When Moving Your House

When it comes to moving a house, we suggest that you follow some common but important packaging tips. In other words, if you follow these common hacks, you can save a great deal of time money, and energy. Without further ado, let’s take a look at some tips that can help you pack your desired items before they are loaded onto the truck. Read on to know more.

Labe the Items

This is an essential part of the moving process. It is not enough to place general labels on the boxes. What you need to do is label all of the moving boxes based on the content they contain. The label should clearly state what each box contains.

This is important when you are opening up the boxes and taking out all of the items one by one. Besides, it is a great way of keeping a record of all of the items, which will help you save a lot of time and energy.

Pack the Essentials

If some things are required immediately after all of the boxes are unloaded from the truck, make sure you put these items in special boxes. Some good examples of these items include your toothbrush and mobile phone chargers. Generally, this box should contain items that you use on a regular basis.

Pack your Important Items

When it comes to moving a house, make sure you place all of your important documents in the same box. Some examples of these documents include birth and marriage certificates. Make sure that all of these documents are safe and secure.

It is also a great idea to put all your personal documents such as passwords in your personal bag. After all, losing your passport can get you in trouble and make you suffer a lot of headaches.

Packing Heavy Items

As far as packing heavy items is concerned, you have to be much more careful. After all, you don’t want to end up dropping and damaging these items. Besides, carrying heavy items requires that you maintain your balance.

It is better that you hire the services of professional movers if you don’t want to end up damaging heavy items. Also, it is a good idea to place heavy items below all of the other items you have already packed. Also, you may not want to paste labels on all of the boxes that contain heavy and fragile items.

Packaging Fragile Items

As far as packing fragile items is concerned, make sure you be extra careful. It is a great idea to use bubble wraps for packing all of your fragile and expensive items. Once you have packed all of the items, you can stack them vertically to prevent breakage.

Packaging Toiletries

As far as packing cosmetics is concerned, you may want to use a hard cosmetic case. Apart from this, make sure you separate these things with great care. In other words, you need to separate creams and dry items.