Oral Drug Delivery System and Their Advancement

Oral Drug Delivery System and Their Advancement

Oral drug delivery systems in animals have evolved significantly, transforming the way medications and treatments are administered to various species. From domestic pets to livestock, the advancement of oral drug delivery systems has improved the efficacy, safety, and convenience of veterinary medications. In this essay, we will explore the importance of oral drug delivery systems in animals, their evolution, and the significant advancements that have enhanced animal healthcare.

Drug delivery is the method or process of administering a pharmaceutical compound to achieve a desirable therapeutic effect in humans or animals. Drug delivery technologies modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. Drug Delivery System can be defined as a formulation or a device that enables the introduction of a therapeutic substance in the body and improves its efficiency and safety by controlling the rate, time and place of release of drugs in the body. A drug delivery system comprising of a drug formulation, a carrier (medica device or dosage form/technology to carry the drug inside the body) and a mechanism by which the drug is released into the body. An effective drug delivery system eliminates loss of drug while passing through biological barriers and carries it to the target to achieve the desirable therapeutic effect.

What is the need for the advanced drug delivery system?

The drugs are normally not required or essential for the life of healthy organism, so they are considered as foreign substance (xenobiotic) and ultimately the body tries to eliminate them by various natural passive or active processes. Conventional drug delivery involves the formulation of the drug into a suitable form, such as a compressed tablet for oral administration or a solution for intravenous administration. So the administered drug should face various biological barriors and catabolic enzymes before it reaches its target place. Some orally administered drugs are largely ionized and so absorbed only in a pH specific site or can be destroyed in acidic or alkaline pH (pH sensitive), host enzymes can destroy nearly all the orally administered protein drugs. It increases amount of drug to be administered to reach its therapeutic concentration at its target site. Some drugs are low in their margin of safety and can produce toxic effect well before its therapeutic effect. A drug may be life saving but poor pharmacokinetic profile will prevent its usage. This necessitates the advanced drug delivery system to improve therapeutic efficacy, targeted action, reduce the loss during transport in the biological system with no or very less adverse effects.

Principles of drug delivery system

A good drug delivery system should aims to produce maximum therapeutic benefits with minimum toxicity, it should not be recognized by the immune system and the drug should be delivered at the targeted site to avoid toxicity to the other normal cells. Controlled release or phased release or sustained release is important for the drugs with low bioavailability and less margin of safety. Such drugs should be released to the target in a controlled manner to get steady state concentration for prolonged period of time. Conventional drug delivery system can be classified into non-invasive and invasive, the former includes oral, sub mucosal, sub lingual, nasal, ocular, otic , pulmonary (inhalation), topical, transdermal, colorectal, vaginal, urethral and the latter includes parenteral routes like intra-venous, intra-muscular, subcutaneous, intra-dermal, intrathecal, epidural, intragastric/intraruminal. Conventional drug delivery system developed to increase bioavailability of the drug but one should consider that, although it is one of the factors which influence the therapeutic efficacy of the drug, it lacks the targeted, sustained drug delivery.

Advanced Drug Delivery System

Advancement in drug delivery system viewed to develop more precised drug delivery system which targets and releases the drug only at the site of requirement. It can be of passive targeting which uses the passive mechanisms like phagoctosis by reticulo endothelial cells, M-cells, endocytosis, micronization for trans or intercellular passage and active targeting which include, Liposome, Microspheres, Drug- Protein conjugates, Erythrocytes, Dendrimers, Nanoparticles, Nanofibers, Nanotubes, Vector based drug delivery etc.

Importance of Oral Drug Delivery Systems in Animals

1. Convenience and Compliance: Oral drug delivery is one of the most convenient methods for administering medications to animals, as it is less invasive and generally easier to manage than injections or other routes.
2. Painless Administration: Many animals find oral administration less stressful and painful than injections, making it a preferred method for both veterinarians and animal owners.
3. Wide Applicability: Oral drug delivery systems are versatile and applicable to various animal species, from dogs and cats to livestock, wildlife, and exotic animals.
4. Chronic Medication: For chronic conditions that require long-term medication, oral delivery systems are often more practical and sustainable.

Evolution of Oral Drug Delivery Systems

1. Traditional Oral Medications: Traditional tablets, capsules, and liquids were the primary oral drug delivery forms for animals. However, these have limitations in terms of dosage accuracy and palatability.
2. Oral Suspensions: Liquid formulations, including suspensions and solutions, offer more precise dosing for small animals and are often flavored to enhance palatability.
3. Pharmaceutical Advances: Advancements in pharmaceutical technology have led to the development of more sophisticated drug delivery systems, including controlled-release formulations and oral transmucosal systems.

III. Advancements in Oral Drug Delivery Systems

1. Oral Transmucosal Drug Delivery: This innovative approach allows for drug absorption through the oral mucosa, bypassing the digestive system. It provides rapid drug uptake and is particularly valuable for emergencies or when an animal cannot swallow.
2. Controlled-Release Formulations: These formulations release medication gradually over an extended period, reducing the frequency of dosing and improving compliance for chronic conditions.
3. Flavor Enhancements: Many modern oral medications for pets are available in flavors that animals find appealing, making administration more convenient.
4. Pharmaceutical Coating Technologies: Advances in pharmaceutical coatings improve the taste masking of bitter or unpalatable medications, making them more acceptable to animals.
5. Nanoparticles and Nanocarriers: Nanotechnology is being employed to enhance drug solubility, stability, and bioavailability in oral formulations, improving drug efficacy.
6. Dose Accuracy and Precision: Precise dosing is crucial, especially in veterinary medicine. Advancements in manufacturing techniques ensure accurate and consistent dosages, reducing the risk of under- or overdosing.

Challenges and Considerations

1. Palatability: Ensuring that medications are palatable to animals is essential for compliance. Flavor enhancement and taste masking are critical considerations.
2. Species-Specific Formulations: Different animals may have unique needs and responses to oral medications. Tailoring formulations for specific species is crucial.
3. Safety and Efficacy: The safety and effectiveness of oral drug delivery systems must be rigorously tested and proven for each intended use.
4. Regulatory Compliance: Adhering to regulatory requirements and quality control standards is essential to ensure the safety and efficacy of animal medications.

Recent advances in the oral drug delivery system:

1. Muco adhesive buccal drug delivery (Thin film drug delivery/ dissolving film/oral drug strip) In this system the drug formulation adsorbed in to the thin film of polymers which rapidly dissolves when it contacts the mucosa and releases the drug. This is used for the OTC drugs which have the high oral absorption profile. Different buccal delivery products have been marketed or are proposed for certain diseases like trigeminal neuralgia, Meniere’s disease, diabetes, and addiction. This method also having the scope of delivers the oral vaccines.

2. Osmotic Controlled Release Oral Delivery System (reservoir system) Osmotic controlled drug delivery system, deliver the drug in a large extent and the delivery nature is independent of the physiological factors of the gastrointestinal tract and these systems can be utilized for systemic as well as targeted delivery of drugs. Osmotic Pump Controlled Release Preparation is a novel drug delivery system with eternally drug delivery rate as characteristic and controlled with the osmotic pressure difference between inside and outside of the semipermeable membrane as drug delivery power for controlled delivery of active agents. Basically it consists of an osmogen (osmotic agent), a wicking agent to draw water inside, covered by a rate limiting membrane, coated by a flux regulator and a pore forming agent (after contact with fluid leaches out and forms pore) for the delivery of drug in a controlled manner stated as zero order release of drug. Once the tablet comes in contact with the aqueous environment, the water-soluble component dissolves and an osmotic pumping system can activate. Subsequently, water diffuses into the core through the micro porous membrane, setting up an osmotic gradient and thereby controlling the release of drug. Slight modification on this drug delivery system can make site specific drug delivery. e.g. Enteric coating can be used for the colon targeted drug delivery.

3. Matrix System

In matrix systems the drug homogeneously distributed within the polymer is dissolved, dispersed or dissolved and dispersed in order to achieve controlled drug release or involves the direct compression of blend of drug, retardant material and additives to formulate a tablet in which the drug is embedded in a matrix of the retardant. Alternatively drug and retardant blend may be granulated prior to compression. These systems present several advantages as easy-manufacture and low cost, lower risk of dose dumping and the possibility of improvement of aqueous drug solubility. Besides, drug-polymer interactions can occur and bring benefits in terms of mechanical properties such plasticizing effect. The materials most widely used in preparing matrix systems include both hydrophilic and hydrophobic polymers. Commonly available hydrophilic polymers include Hydroxypropylmethylcellulose (HPMC), Hydroxypropylcellulose (HPC), Hydroxyethyl cellulose (HEC), Xanthan gum, Sodium alginate, Poly (ethylene oxide) and cross-linked homopolymers and copolymers of Acrylic acid. the matrix drug formulation start releasing the drug when contacts the fluid, drug outside matrix leaves out first by forming pore and it make the channel for the drug in deep layer to come out.

4. Phased Drug Delivery Matrix system can be a monolayer or multilayer (mixture of different polymers) which explains the time dependant drug delivery (fast and slow release).multi layer matrix system may contain different type of drug formulations which can be released at different time intervals (e.g. Verelan PM ™). Capsules contains the drug mixed with hydrophilic and hydrophobic polymers first one dissolves, releases the drug immediately and hydrophobic polymers start releasing the drug after passing the particular time interval. Conversely it may contain a drug core covered by semi permeable membrane which allows high drug loading this eliminates the disadvantage of conventional matrix system.

4. Gastro Retentive Delivery Gastro retentive systems can remain in the gastric region for several hours and hence significantly prolong the gastric residence time of drugs. Prolonged gastric retention improves bioavailability, reduces drug waste, and improves solubility for drugs that are less soluble in a high pH environment. It has applications also for local drug delivery to the stomach and proximal small intestines. Gastro retention helps to provide better availability of new products with new therapeutic possibilities and substantial benefits for patients Several techniques, including floating, swelling, inflation, and adhesion have been explored to increase the gastro-retention of dosage forms. The floating drug delivery system and bioadhesive drug delivery are widely used technique for gastro-retention. The floating systems in particular have been extensively researched, mainly because it does not adversely affect the motility of GI tract. Other types of gastro retentive systems are Gas generating system, raft forming system, low density system, bioadhesive system, hydro dynamically balanced system, swelling system, high density system (hydro gel) and magnetic system.

5. SMEDDS Self Micro Emulsifying Drug Delivery System (SMEDDS) employs drug intrinsic activity known as ouzo effect, is oil-in-water micro emulsion that formed when strongly hydrophobic oil mixed with water miscible solvents like ethanol. SMEDDS formulations are isotropic mixtures of an oil, a surfactant, a co-surfactant (or solubilizer), and a drug. The basic principle of this system is its ability to form fine oil-in-water (o/w) micro-emulsions under gentle agitation following dilution by aqueous phases (i.e., the digestive motility of the stomach and intestine provide the agitation required for self-emulsification in vivo in the lumen of the gut). This spontaneous formation of an emulsion in the gastrointestinal tract presents the drug in a solubilized form, and the small size of the formed droplet provides a large interfacial surface area for drug absorption. It is more stable than other emulsions and also has some commercial applications like increased bioavailability and reduced production cost and dose of the drug.

Conclusion

Advancements in oral drug delivery systems have revolutionized animal healthcare, making it more convenient, efficient, and less stressful for both animals and their caregivers. The development of controlled-release formulations, oral transmucosal systems, flavor enhancements, and other innovations has improved the precision of dosing and the palatability of medications for animals. These advancements have contributed to better compliance and treatment outcomes, ultimately enhancing the health and well-being of animals in veterinary medicine. As technology and pharmaceutical research continue to progress, the future of oral drug delivery systems in animal healthcare holds the promise of even more effective and tailored treatment options.

 Compiled  & Shared by- This paper is a compilation of groupwork provided by the

Team, LITD (Livestock Institute of Training & Development)

 Image-Courtesy-Google

 Reference-On Request.

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