(167aa) Polymers Membrane Technology for Controlled Drug Delivery System

In controlled drug delivery system, a polymer membrane is used to moderate the rate of delivery of drug to the body. In some devices the membrane controls permeation of the drug from a reservoir to achieve the drug delivery rate required. Other devices use the osmotic pressure produced by diffusion of water across a membrane to power miniature pumps. In yet other devices the drug is impregnated into the membrane material, which then slowly dissolves or degrades in the body. Drug delivery is then controlled by a combination of diffusion and biodegradation. For the last decades, injectable hydrogels have gained considerable attention in biomedicine fields including controlled drug delivery system. Thermosensitive hydrogels N- isopropylacrylamide copolymer and Pluronic copolymer were the most important ones, because they were flowing liquid at or below ambient temperatures. Oral controlled drug delivery system can provide continuous delivery of drugs at controlled rate and predictable kinetics throughout the gastrointestinal transit. Drug release could also be controlled and maintained at therapeutic levels, by adjusting the composition of the nanoparticle system. They could even facilitate the combined therapy by the incorporation of more than one active ingredient. When considering the preparation of polymeric nanoparticles, the use of surfactants may be a requirement. Surfactants are amphiphilic organic molecules that can self- assemble in solution. Most used surfactants are composed by a hydrocarbon chain(hydrophobic section) bound to an ionic functional group(forming the so- called cationic surfactants, such as benzalkonium chloride or tetramethylammonium hydroxide or anionic surfactants, like sodium laurate). Non- ionic surfactants can also be found, in which the amphiphilic character is generated by the union of hydrophobic and hydrophilic molecules(for example, ethoxylated amines, alkyl and non- alkyl phenol ethoxylates). The synthetic polymer based on N-(2-hydroxypropyl) methacrylamide copolymers are recognized drug carriers with unique properties that nominate them among the most serious nano medicines for human clinical trials. The objective of all these devices is to deliver a drug to the body at a rate predetermined by the design of the device and independent of the changing environment of the body. In conventional medications, only the total mass of drug delivered to a patient is controlled. In control drug delivery, both the mass and the rate at which the drug is delivered can be controlled, providing three important therapeutic benefits: 1)the drug is metered to the body slowly over a long period; therefore, the problem of overdosing and under dosing associated with conventional periodic medication is avoided, 2)the drug is given locally, ideally to the affected organ directly, rather than systemically as an injection or tablet. Localized delivery results in high concentrations of the drug at the site of action, but low concentrations and hence fewer side effects elsewhere, 3)as a consequence of metered, localized drug delivery, controlled release devices generally equal or improve the therapeutic effects of conventional medications, while using a fraction of the drug. Thus, the problems of drug related side effects are correspondingly lower. The concept of controlled delivery is not limited to drugs. Similar principles are used to control the delivery of agrochemicals, fertilizers and pesticides, for example, and in many household products. Membrane diffusion-controlled systems: membrane diffusion-controlled systems, a drug is released from a device by permeation from its interior to the surrounding medium. The rate of diffusion of the drug through the membrane governs its rate of release. An inert membrane enclose the drug to be released; the drug diffuses through the membrane at a finite, controllable rate. If the concentration(or thermodynamic activity) of the material in equilibrium with the inner surface of the enclosing membrane is constant then the concentration gradient, the driving force for diffusional release of the drugs, is constant. This occurs when the inner reservoir contains a saturated solution of the material, providing a constant release rate for as long as excess solid is maintained in the solution. This is called zero- order release. If, however, the active drug within the device is initially present as an unsaturated solution, its concentration falls as it is released. The release rate declines exponentially, producing a first-order release profile. Biodegradable systems: the diffusion-controlled devices outlined so far are permanent, in that the membrane or matrix of the device remains implanted after its delivery role is completed. In some applications, particularly in the medical field, this is undesirable; such applications require a device that degrades during or subsequent to its delivery role. Many polymer-based devices that slowly biodegrade when implanted in the body have been developed; the most important are based on polylactic acid, polyglycolic acid and their copolymers. In principle, the release of an active agent can be programmed by dispersing the material within such polymers, with erosion of the polymer effecting release of the agent. One class of biodegradable polymers is surface eroding; the surface area of such polymers decreases with time as the conventionally cylindrical- or spherical-shaped device erodes. This results in a decreasing release rate unless the geometry of the device is appropriately manipulated or the device is designed to contain a higher concentration of the agent in the interior than in the surface layers. In a common class of biodegradable polymer, the initial period of degradation occurs very slowly, after which the degradation rate increases rapidly. Biodegradable and low molecular weight poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) triblock copolymers successfully synthesized. Osmotic systems: osmotic effects are often a problem in diffusion-controlled systems because imbibition of water swells the device or dilutes the drug. In osmotic drug delivery system containing antibiotic drugs, the porous osmotic pump tablets with agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as excipients. Drug release could also be controlled and maintained at therapeutic levels, by adjusting the composition of the nanoparticle system. They could even facilitate the combined therapy by the incorporation of more than one active ingredient. When considering the preparation of polymeric nanoparticles, the use of surfactants may be a requirement. Surfactants are amphiphilic organic molecules that can self- assemble in solution. Most used surfactants are composed by a hydrocarbon chain (hydrophobic section) bound to an ionic functional group(forming the so- called cationic surfactants, such as benzalkonium chloride or tetramethylammonium hydroxide or anionic surfactants, like sodium laurate). Non- ionic surfactants can also be found, in which the amphiphilic character is generated by the union of hydrophobic and hydrophilic molecules (for example, ethoxylated amines, alkyl and non- alkyl phenol ethoxylates). Self-assembling block copolymers (Polyethylene glycol/Poly lactic acid and Polyethylene glycol/Poly lactic-co- glycolic acid block copolymers, Polyethylene glycol/polycaprolactone, polyether modified poly(acrylic acid) with large solubility differences between hydrophilic and hydrophobic moieties have the property of forming temperature dependent micellar aggregates and, after a further temperature increase, of gel formation due to micelle aggregation or packing. The use of nanoparticle for ophthalmic and oral delivery was investigated. Poly lactic-co-glcolic acid has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. In the course of the developments of a new drug delivery concept, four thermosensitive copolymers of poly(N-isopropylacrylamide), with phase transition temperature slightly higher than 37℃, were synthesized and used as time- controlled drug delivery agents. For this purpose, compression-coated tablets coated with the thermosensitive copolymers and containing Na₂SO₄ were prepared and in vitro dissolution tests were performed at constant physiological temperature, the lag time before drug release being controlled by the amount of Na₂SO₄ incorporated into the form. A drug (active pharmaceutical ingredients) is a substance recognized in official pharmacopoeia intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease as per the FDA. Drug delivery is a technique of delivering medication to a patient in such a manner that specifically increases the drug concentration in some parts of the body as compared to others. The ultimate goal of any delivery system is to extend, confine and target the drug in the diseased tissue with a protected interaction. Every dosage form is a combination of drug/ active pharmaceutical ingredients and the non-drug component called excipients/additives. Active pharmaceutical ingredients are the actual chemical components used to treat diseases. Generally, drug delivery systems are preferred because direct clinical use of the active drug substances “as they are” is very rare due to several reasons: active pharmaceutical ingredients handling and accurate dosing can be difficult or impossible for very potent drugs (for example, low mg and µg doses). Administration of drugs into the body cavities can be impractical and unfeasible as they can be degraded at the site of administration (for example, low pH in the stomach) and may cause local irritations or injury when the drug concentration is high at the site of administration. Some active pharmaceutical ingredients are sensitive to the environment and can benefit from reducing the exposure to environment factors (light, moisture, temperature and pH), or they need to be chemically stabilized due ti the inherent chemical instability. Active pharmaceutical ingredients have unpleasant organoleptic qualities(taste, smell and compliance), which reduce patient compliance.