Development of Controlled Drug Delivery Systems (CDDS)

Development of Controlled Drug Delivery Systems (CDDS)1.1 CONTROLLED DRUG actors line SYSTEMS (CDDS)Now a twenty-four hour periods on the breeding of newfangled do medicates voice communication arrangements (NDDS) marked consideration has been foc single-valued functiond. The method of point economy to the site of action shows a signifi sack upt effect on its efficacy. It leads to the development and evolution of novel medicate address systems that enhanced per mildewance of electromotive force dose tittles. Novel dose pitch shot systems play a let on role in pharmaceutical investigate and development. Since when compared new chemical mediety the developmental personify and time required for introducing NDDS is relatively low.Oral pass remains hotshot of the most natural r come verbotenes of drug validation and has seen infrequent accomplishments in the last couple of decades towards optimization of impromptu carry throughy of drug molecules. Oral ing estion is one of the oldest and most extensively utilise routes of drug administration. They provide an effective method of obtaining systemic and local effects.Drug voice communication describes a process whereby a sanative agent is administered to the body in a figureled manner. The products commercial and clinical value, product specialization can buoy be improved by developed drug saving technologies. These advanced technologies serve as an advanced resource to outreach the competition. By simplifying the administration and dosing regimen drug delivery technologies make medicine more than satisfactory and convenient to a patient.Any drug molecule by victimisation Novel drug delivery system (NDDS) can get a new life, and thus improving the competitiveness, patent life and market value. Among distinguishable NDDS present in the market, the major share in the market is consort by the oral controlled rel fill-in systems because of its greater benefits of patient complianc e and ease of administration. The development of novel and highly versatile delivery systems and osmotic drug delivery systems are the major contribution in oral NDDS.Basically, thither are three novel modes of drug delivery, i.e.Targeted delivery,Modulated relax andControlled release.Targeted delivery refers to the administration of a drug carrier systemically in order to deliver drug to the specific type of cells, tissues or organs. Modulated release implies use of a drug delivery thingamajig that releases the drug under controlled environmental conditions, bio feedback, sensor input or an external control device at a variable esteem. Controlled release refers to a specific device that delivers the drug at specific release profiles or at a mold rate into the patient body.1.1 CONTROLLED DRUG DELIVERY SYSTEMS (CDDS)The nature of the controlled release back breaker nervous strain is such that the release is determined by the flesh of the system and the physiochemical propertie s of the drug and is in appearent of the external factors or the microenvironment in which the dosage form is placed. These products typically provide significant benefits over immediate-release conventional dosage formulations. optimum therapy with repetitive administration of conventional dosage forms (e.g. injectables, liquids or tablets) can classically be pursued by dosage scheduling. The aim of this process is to prevent drug parsimony in a therapeutic range, above the negligible effective stringency and below the toxic concentration.Thus CDDS avoids the undesirable truism tooth characteristics of the plasm concentration vs time profiles of the conventional drug products.A delineate illustration of controlled versus conventional dosage delivery is shown in Figure-1.Fig 1.1 plasm Time profile of controlled drug release and conventional releaseThe plasma concentration of the drug reaches a maximum (crest) with conventional dosage forms and past decrease (trough) at the point where repeated administrations becomes necessary to maintain the plasma drug concentration. Very lots the initial concentration is above the therapeutically effective level that may increase the risk of side effects. effected dosage forms can thus result in a drug regimen in which the drug concentration oscillates between alternating fulfilments of dose and inefficiency.The delivery of drug at controlled rate over an extended period of time is represented mathematicallyRate in = Rate out = Ke x Cd x VdWhere Cd is the desired drug level, Vd is the volume of distribution and Ke rate content for drug riddance from the body.Added to this, the high cost of development of new, safe, specific and effective drug molecule is prohibitive and developing nations virtually cannot afford such integrated multi-group cost intensive drug development ventures. Therefore, many pharmaceutical industries and drug research institute oriented their efforts to develop pre-programmed unattended d elivery of drug at a rate and for a period to meet and achieve the therapeutic need. These systems are coined as Controlled drug delivery systemsTable 1.1 Classification of oral controlled release systems depending on mechanism ofRelease 3 (vyas etal,2002)1.1.1. ADVANTAGES OF CONTROLLED RELEASE PRODUCTS 4As controlled release dosage form are slightly pricy than conventional formulations, they cannot be justified unless they offer come clinical or practical advantages given belowReduction in dosing frequencyto a greater extent uniform effectReduced fluctuation in steady levels change magnitude safety margin of high potency drugsImproved patient restroom and complianceReduced in total amount of dose administered turning away of night time dosingReducing of GI irritation and another(prenominal) dose related side effects andReduction in health palm cost.1.1.2.DISADVANTAGES OF CONTROLLED RELEASE PRODUCTS 4However, controlled drug delivery systems also have virtually disadvantages. They include,High costPoor systemic avail cogencyUnpredictable and often poor invitro-invivo correlationPossibility of dose dumpingDosage adjustments say-so is reducedFirst pass clearance potential is increasedIn case of hypersensitivity reactions, toxicity or poisoning drug retrieval is rockyEffect of oral dose depends on Mean Residence Time.To control or change the drug release from a dosage form there will be a tally of design options. close to of the per oral controlled release dosage forms comes under the category of osmotic, matrix or rootage systems. The polymer matrix contains embedded drug in matrix systems in which the release occurs by partitioning of drug into the release medium and polymer matrix. In case of reservoir systems a rate controlling tissue layer is skirt and coated around the drug core. But, drug release from conventional controlled systems i.e., reservoir and matrix systems is affected by various factors like presence of food, pH and different physiol ogical factors. In case of osmotic systems the drug is delivered establish on the rulers of osmotic closet. The drug release from this system doesnt depend on the pH and various physiological parameters and thus by optimizing the drug and systems properties the release characteristics can be modulated.1.2. OSMOTIC DRUG DELLIVERY SYSTEMS A suss out1.2.1. HISTORICAL BACKGROUNDIn 1955 Rose and Nelson utilized the principles of osmotic storm in drug delivery for the first time. They described two systems one that delivered 0.02 ml/day for 100 days and another that delivered 0.5 ml/day for 4 days, both for use in Pharmacological research.In the 1970s, Higuchi and Leeper proposed a series of variations of the Rose-Nelson pump5. Theeuwes further modified the Rose-Nelson pump and developed a system. teentsy osmotic pumps of these forms are sold under the trade name ALZET (Alza Corp., CA). The device has a volume of approximately 170l, and the normal delivery rate is 1l/hr.A major mile stone was achieved in 1974 with the translation by Theeuwes and Alzas co-workers of a tablet design composed of a compressed tablet-core surrounded by a trucking rig permeable membrane with a single orifice, so-called Elementary osmotic pump (EOP). This design adaptation for human use was conveniently processable using standard tabletting and coat procedures and equipment. The first two products indomethacin, Osmosin6 and phenylpropanolamine, Acutrim TM6 were launched in the 1980s.Oral osmotic drug delivery system (OODS) development continued with two new OODS designs, the controlled-porosity osmotic pumps (CPOP) and the push-pull osmotic pumps (PPOP). The first of these was the CPOP, which was designed to decrease the risk of extremely localized drug-induced irritation at the site close to the orifice.In the 2000s, a new drug product based on OODS technology was formulated to deliver methylphenidate to children (above the age of 6 years) with attention-deficit hyperactivity diso rder (ADHD). These delivery systems were based on a new design, the push-stick osmotic pumps (PSOP), which combined immediate and sustained drug release phases.The drug release from this system doesnt depend on the pH and various physiological parameters and thus by optimizing the drug and systems properties the release characteristics can be modulated. In the last few years more number of patents are granted on these oral omotic drug delivery systems. These systems has ability to improve therapeutic agents clinical profile and so they are go one of the most attr combat-ready technologies today.osmotically controlled oral drug delivery system for the controlled delivery of active agents follows osmotic pressure principle. For the controlled drug delivery osmotic devices are most assured strategy based systems. Among the controlled drug delivery systems these are most reliable systems. osmotic systems could be used in the form of implantable devices or oral drug delivery systems. Os motic pump tablet (OPT) generally consists of a core including the drug, an osmotic agent, other excipients and semi-permeable membrane coat.1.2.2. THEORYOsmosis can be defined as spontaneous movement of a result from a solution of lower solute concentration to a solution of higher solute concentration through an ideal semi permeable membrane, which is permeable only to the solvent and impermeable to solute. The pressure utilize to the higher-concentration side to inhibit solvent flow is called osmotic pressure8.Osmotic pressure is a colligative property, which depends on concentration of solute that contributes to osmotic pressure. Solutions of different concentrations having the same solute and solvent system exhibit an osmotic pressure proportional to their concentrations. Thus a constant osmotic pressure, and thereby a constant influx of wet supply can be achieved by an osmotic delivery system that results in a constant zero order release rate of drug8. doctrine OF OSMOSISAn osmotic system releases a therapeutic agent at a predetermined, zero order delivery rate based on the principle of Osmosis, which is movement of a solvent from lower concentration of solute towards higher concentration of solute across a semi-permeable membrane.When osmotic system is administered, from the one or more delivery ports the drug that contain suspension or solutions is pumped out of the core due to the hydrostatic pressure developed by the drunkenness of water in to the core osmotically through the semi-permeable membrane. By the water influx through semi-permeable membrane the delivery of drug from this system can be controlled.Osmotic pressure is directly proportional to temperature and concentration and the future(a) equation describes the relation between them = cRTwhereOP = osmotic pressure, = osmotic coefficient,c = molar concentration,R = gas constant,T = Absolute temperature.OSMOTIC PUMPSOsmotic pump is a new delivery device, which delivers drugs or other acti ve agents at a controlled rate by the principle of osmosis. Control resides in the water permeation properties of the formulationsTable 1.2 Examples of some marketed band of Osmotic drug delivery system7DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY, SVCPPAGE 1