{'fraction_non_alphanumeric': 0.021111421390672996, 'fraction_numerical': 0.005752583077352695, 'mean_word_length': 5.113349265961079, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
A Comprehensive Review on Osmotic Controlled Drug Delivery System

The conventional drug delivery systems provide an immediate release of the drug in which the release of the drug cannot be managed and the effective concentration at the target site cannot be sustained for a longer time. This form of dosage pattern can lead to plasma concentration fluctuation. Osmotic systems are the most effective strategy-based drug delivery control system. They work on the osmotic pressure principle to control the drug's delivery. The release of the drug is largely independent of the GIT's physiological factors. Such processes use osmosis as the main driving force for the release of drugs. For the osmotic drug delivery system, adequate water solubility of the drug is necessary. Osmotic drug delivery systems are composed of a drug core that is osmotically active and surrounded by a semi-permeable membrane. Numerous formulation factors such as osmotic pressure of the core component(s), solubility and size of the delivery orifice, and the nature of semi-permeable membrane influence drug(s) release from osmotic systems. This review offers a brief description of components, ideal drug characteristics, types of osmotically regulated pump and its mechanism, advantages, disadvantages.


INTRODUCTION
Oral drug delivery is the most favored and convenient option since the oral route offers maximum active surface area for the administration of various drugs among all drug delivery systems. 1 There is little or no control over the release of the drug in conventional oral drug delivery systems and successful concentration can be achieved at the target site through the irregular administration of excessive dose. The consequence of this form of dosage pattern results in fluctuation of concentrations of therapeutic plasma, contributing to some significant side effects. In addition, the rate and degree of drug absorption from conventional dosage forms can vary greatly depending on factors such as excipient presence, physicochemical properties of the medicat ion, various physiological factors such as the presence or absence of food, pH of the GIT tract, gast rointestinal motility, etc. Local gastrointestinal or systemic toxicity can be caused by uncontrolled rapid release of the drug. Therefore, different approaches are taken in the design of formulations that will overcome the disadvantages of conventional dosage forms, including a sustained/controlled system of drug delivery. There are three major groups of drug delivery controlled; trans-dermal, intravenous and oral route. 2 Oral osmotic controlled release (CR) delivery systems uses osmotic pressure to control active agent distribution. 3 Substance release from these systems is largely independent of pH and other physiological parameters and by modifying the properties of substance and system it is possible to modulate the release characteristics. 2 The first to create an oral osmotic pump was the U.S. Alza Corporation R.
History of osmotic drug delivery system: 4 About 75 years after the discovery of the principle of osmosis, the drug delivery systems were clearly designed. The Australian scientists Rose and Nelson were initiators of the delivery of osmotic drugs. In 1955 an implantable pump was developed, consisting of three chambers: a drug chamber, a salt chamber containing excess solid salt, and a water chamber. In 1975-the introduction of the elementary osmotic pump for oral drug delivery. The pump is a drug-containing osmotic core surrounded by a semi-permeable membrane with a delivery orifice. When this pump is exposed to water, the core osmotically absorbs water at a regulated rate, defined by the water permeability of the membrane and the core formulation osmotic pressure. Since the membrane cannot be expanded, the increase in volume caused by water imbibition leads to the development of hydrostatic pressure within the tablet. This pressure is eased through the delivery orifice by the flow of saturated solution out of the device. In the 1970s, implantable osmotic pumps were a major In addition to the overall advantages of controlled drug delivery systems, osmotic pumps have some unique advantages as follows: 1. Drug delivery from osmotic pumps can be configured to obey the true kinetics of zeroorder.
2. Delivery, if needed, can be delayed or pulsed.
3. Drug release is independent of the body's gastric pH and hydrodynamic conditions from osmotic pumps.
4. Higher release rates from osmotic systems are possible than with conventional drug delivery systems based on diffusion.
5. By modulating the release control parameters, the delivery rate of drugs from these systems is highly predictable and programmable 6. It is possible to obtain a high degree of differentiation between In vitro and In vivo from osmotic pumps.
7. The quality of food is minimally impaired by the release of drugs from osmotic processes.

Semi-Permeable Membrane:
Since the membrane in osmotic systems is semi-permeable in nature, it is possible to select any polymer that is permeable to water but impermeable to solute. 12

Hydrophilics and Hydrophobics Polymers:
These polymers are used to formulate osmotic systems to make drugs that contain the core of the matrix. The extremely water-soluble compounds can be concentrated in hydrophobic matrices, and compounds that are moderately water-soluble can be concentrated in hydrophilic matrices for more controlled release. Mixtures of hydrophilic and hydrophobic polymers were commonly used in the formulation of water-soluble drug osmotic pumps. 16 The selection is dependent on the drug's solubility and the amount and rate of drug to be released from the pump. The polymers are either swellable or non-swellable in nature. In the pumps containing relatively water-soluble drugs, swellable polymers are mostly used. Because of their swelling nature they increase the hydrostatic pressure inside the pump, the non-swellable polymers are used for highly water-soluble drugs. 17 Ionic hydrogels such as sodium carboxy methyl cellulose are usually used due to their osmogenic property. Through integrating these polymers into the formulations, more precise controlled release of drugs can be achieved. For this reason it is possible to use hydrophilic polymers such as hydroxy ethyl cellulose, carboxy methyl cellulose, hydroxy propyl methyl cellulose, high molecular weight poly (vinyl pyrrollidone) and hydrophobic polymers such as ethyl cellulose and wax materials. 18

Wicking Agents:
A wicking agent is described as a material capable of drawing water into a distribution device's porous network. The wicking agents are those agents that assist with the incoming aqueous fluid to improve the drug's contact surface area. Using the wicking agent helps improve the drug output released from the drug's orifice. A wicking agent has a swellable or non-swellable character. 19 They are distinguished by being able to withstand water physisorption. Physisorption is a type of absorption where the solvent molecules may bind loosely to the wicking agent's surfaces through Vander Waals interactions between the wicking agent's surface and the adsorbed molecule. The wicking agent's role is to carry water to surfaces inside the tablet's core, thus creating channels or an increased surface area network. 20 Sources are silicon dioxide colloidal, PVP and lauryl sulfate sodium.

Solubilizing Agent:
Highly water-soluble drugs would demonstrate a high release rate of zero order for the osmotic drug delivery system. Most drugs with low intrinsic solubility in water are therefore poor candidates for osmotic delivery. However, the solubility of drugs can be modulated in the core.
Adding solubilizing agents to the core tablet dramatically increases the solubility of the drug. 21 Classification of Non-swellable solubilizing agents: (i) agents that inhibit drug crystal formation or otherwise act by drug complexation (e.g., PVP, poly(ethylene glycol) (PEG 8000) and βcyclodextrin), (ii) a high-HLB micellular surfactant, particularly nonionic surfactants (e.g., 20, 60-80 polyoxyethylene or surface-containing polyethylene). Combinations between complexing agents such as polyvinyl pyrrolidone (PVP) and poly(ethylene glycol) and anionic surfactants such as SLS are usually preferred.

Osmogens: 22
Osmogens are an essential component of the formulations of osmotic. When the biological fluid gain access through the semi permeable membrane into the osmotic system, osmogens are dissolved in the biological fluid, which causes osmotic pressure buildup inside the pump and forces medicinal products outside the pump through the delivery orifice. These include inorganic salts and carbohydrates. Osmogens are commonly used to achieve maximum osmotic pressure within the device. Eg: -Sodium chloride and potassium chloride.

Surfactants. 23
The addition of surfactants to the wall-forming material is particularly useful. They produce an integral composite that can be used to make the device's wall operational. The surfactants act by regulating the surface energy of materials to improve their mixture into the composite during the drug release period and maintain their integrity in the use environment. Typical surfactants such as polyoxyethylene glyceryl ricinoleate, polyoxyethylene castor oil containing ethylene oxide, glyceryl laurates, and glycerol (sorbitone oleate, stearate, or laurate) are included in the formulation.

Coating Solvents: 23
Solvents suitable for producing a polymeric solution used to make the osmotic wall involve neutral inorganic and organic solvents that do not damage the core and other materials. Methylene

Plasticizers.
To modify the physical properties and improve film-forming characteristics of polymers, plasticizers or low molecular weight diluents are added in pharmaceutical coatings. Plasticizers can significantly change the visco-elastic behavior of polymers. 24 Plasticizers can turn a hard and brittle polymer into a softer, more flexible material and possibly make it more mechanical stressresistant. 9 Plasticizers reduce the temperature of the wall's second order-phase transition or the These agents are particularly used in pumps designed for poorly water-soluble drugs and osmotic pumps for in the development of controlled porosity or multiparticulate. 27 These pore-forming agents cause microporous membrane formation. The microporous wall may be formed in situ by the leaching of a pore-former during system operation. By fact, the pore-formers can be either inorganic or organic, solid or liquid. For example, alkaline metal salts such as sodium chloride, sodium bromide, potassium chloride, potassium sulphate, potassium phosphate, and so on, alkaline earth metals such as calcium chloride and calcium nitrate, carbohydrates such as , fructose, manose, lactose, sorbitol and mannitol, sucrose, glucose and diols and polyols such as polyhydrates, polyethylene glycols, and polyvinyl pyrrolids Also used to create pore in the membrane are Triethyl citrate (TEC) and triacetine (TA). The permeability of the membrane to the drug is also improved by the addition of HPMC or saccharose. 28 They was invented the first osmotic pump in 1974. The elementary osmotic pump is a new drug delivery system that delivers the drug at a controlled rate through an osmotic cycle. Control is based on: a) the water permeation characteristics of a semi-permeable membrane surrounding the formulating agent b) the formulation's osmotic properties. This system includes osmotic active agent surrounded by semi-permeable membrane controlling the release rate of the drug. The system is created by using a tableting machine to compress a medication with a sufficient osmotic pressure into a tablet. The tablet is then coated with a semi-permeable membrane, normally cellulose acetate, and a small hole is drilled through the membrane coating (the size ranges from 0.5 to 1.5 mm). the drilling may be done by Mechanical drilling, laser drilling (CO2 laser beam with a wavelength of 10.6μ). 31 When the dosage form is exposed to the aqueous atmosphere, the core absorbs water osmotically at a controlled rate, which is determined by the osmotic pressure of the core and the water permeability of semi-permeable membrane. The volume of saturated drug solution delivered is equal to the volume of solvent uptake. The rate of the system's solvent distribution is constant as long as the excess solid is present inside the device but the rate decreases parabolistically to zero order once the concentration falls below saturation, which is dispensed at a regulated rate from the membrane's delivery orifice. While 60-80% of the drug is released from the Elementary Osmotic Pump Devices (EOP) at a constant rate, a lag time of 30-60 minutes is observed in most cases as the device hydrates until zero order output from the system begins. Such devices are ideal for providing medicines with reasonable water solubility. 32 Chourasia

Controlled Porosity Osmotic Pump:
The pump can be made in single or multi-purpose dosage form, in either form, the delivery system consists of a core of the drug surrounded by a membrane with an asymmetric structure. The membrane consists of a phase inversion process controlled by a mixed solvent system evaporation Membrane is water-permeable, but it is impermeable to solutions and insensitive pore shaping additives that are spread across the surface. Low water-soluble additive amounts are leached from polymer products that were water-permeable but remained insoluble when exposed to water. Then the resulting sponge-like structure formed of interest the controlled porosity walls and was substantially permeable to both water and drug agents dissolved. The release rate of these types of systems depends on the factors such as water permeability of the semi-permeable membrane, the thickness of the coating, the amount of soluble components in the coating, the solubility of the drug in the tablet core and the difference in osmotic pressure across the surface, but is independent

Monolithic Osmotic System:
The monolithic osmotic method is a basic dispersion in polymer matrix of water-soluble agent.
Polymers encapsulate the particles of the drug. When the system comes into contact with the aqueous environment, the active agents ' water imbibitions rupture the polymer matrix capsule that surrounds the drug and thus release it into the external Environment. Initially this process takes place in the outer environment of the polymer matrix, but gradually progresses in a sequential fashion into the inside of the matrix. Such structures control the kinetics of drug delivery in zero order. The osmotic pressure is the main priniciple. 39 The system can be used once or twice a day to administer medications to the colon in a controlled manner. The device is fitted with 5-6 enteric coating and osmotic push-pull units loaded with hard gelatin capsule for controlled delivery of colonic drugs. 41 When gelatin capsule shell dissolves upon contact with GI fluids, the outer shell of the product prevents the entry of fluid from the stomach and dissolves after it reaches the intestine. The water imbibes to the core and the swelling of push compartment takes place. At the same time, the flowable gel is formed that is forced out at a predetermined rate via the delivery orifice. 42 Baker developed a controlled-release delivery system using an osmotic bursting mechanism. The delivery orifice is absent in this system and the orifice scale is small than the standard osmotic system (EOP). When placed in a watery environment, water is absorbed and hydraulic pressure is built up inside until the wall breaks and the contents are released into the environment. The drug release can be controlled by the thickness as well as the area of the semi-permeable membrane.
This method is useful in providing pulsed release. 44 Chourasia

Asymmetrical Membrane Osmotic Tablet:
Asymmetric membrane capsules consists of a product that comprises a center surrounded by a membrane that has an asymmetric structure, i.e. it has a relatively thin, dense region protected by a thicker, porous area. Unlike a conventional gelatin capsule, the capsule wall is made of a waterinsoluble polymer such as cellulose acetate; the asymmetric membrane capsule does not dissolve instantly but provides a sustained release of the active ingredient in the capsule.

Effervescent Osmotic Tablet (EOT):
In this system, the carbon dioxide is formed by effervescent compounds in a dosage form that reacts with acid in the outer environment. This gas expands and dispenses the precipitate drug and

Multiparticulate Delayed-Release System:
Pellets containing a pure drug with or without an osmotic agent are coated with a semi-permeable membrane such as cellulose acetate in this system. Water penetrates into the core when this device comes into contact with the aqueous atmosphere and forms a saturated solution of soluble materials. The gradient of osmotic pressure causes a water flow, leading to rapid membrane expansion and pores formation The release of osmotic ingredients and the drug through these pores tends to follow zero-order kinetics. 50

Self Emulsified Osmotic Tablet:
Self-emulsifying agents were added to the tablet-core composition in the case of slightly soluble or practically insoluble drugs.  vessel fit together tightly. 30 When fluid is immersed in the dispensing device's casing, the osmotic engine expands and exerts pressure on the first and second wall parts connected to the slidable.
The volume of the reservoir containing the active agent is kept constant during the delay time, due to which there is a marginal pressure differential between the reservoir's usage environment and interior. Consequently, the net flow of the environmental fluid driven by pressure enters the reservoir is minimal. 53