Department of Pharmaceutics, Gayatri College of Pharmacy, Sambalpur, Odisha.
A new and very successful method for improving the therapeutic results of oral drugs is Osmotic Controlled Drug Delivery Systems (OSMO) technology. This is especially true when it comes to the treatment of chronic conditions like Type 2 Diabetes Mellitus (T2DM). Regardless of the pH or motility of the gastrointestinal tract, these systems use osmotic pressure to distribute medications in a regulated and prolonged way. The fundamental benefit of OSMO technology is its capacity to keep plasma drug concentrations constant, reducing variations that may result in adverse effects or diminished effectiveness. This results in better glycaemic control, fewer doses, and better patient adherence when it comes to diabetes treatment. Furthermore, extended-release versions of metformin and osmotic systems like Glucotrol XL® (Glipizide) have shown improved tolerability and decreased gastrointestinal side effects, addressing common obstacles to long-term adherence. The components, workings, and clinical advantages of OSMO technology are examined in this abstract, which highlights the technology's expanding significance in enhancing diabetic care and patient quality of life.
Introduction to Oral and Controlled Drug Delivery Systems:
Oral drug delivery remains the most prominent and widely utilized route for systemic drug administration, offering a convenient and efficient means of achieving both local and systemic effects. It is the preferred method due to its ease of administration, improved patient compliance, and lower manufacturing costs. Conventional oral dosage forms are typically designed for immediate drug release and require frequent dosing, which limits their ability to maintain optimal drug concentrations at the target site. Additionally, the bioavailability of drugs can vary significantly depending on several physiological factors such as the presence or absence of food, gastrointestinal (GI) motility, GI pH, and the physicochemical properties of the drug. To overcome these limitations, controlled-release drug delivery systems have been developed, which allow for the predictable and sustained release of drugs. These systems offer numerous advantages over conventional dosage forms, including reduced dosing frequency, enhanced convenience, and improved patient adherence. The primary goal of controlled drug delivery is to maintain a consistent therapeutic level of the drug within the plasma over an extended period, keeping the drug concentration between the minimum effective concentration and the maximum therapeutic concentration. Understanding the principles and mechanisms behind these advanced drug delivery systems is essential, as they can significantly influence therapeutic outcomes. Among the various controlled-release technologies, osmotic controlled drug delivery systems have gained particular attention for their ability to provide prolonged, consistent drug release. This review aims to highlight the key features, mechanisms, and clinical significance of osmotic-controlled drug delivery systems, along with their potential impact on modern pharmaceutical practice [1][2].
Osmotic Drug Delivery Systems:
The most promising strategy-based drug delivery technique to improve drug bioavailability is the osmotic drug delivery system. These systems are driven to release the medicine in a controlled way by osmotic pressure. The net flow of water across a selectively permeable membrane caused by a difference in osmotic pressure across the membrane is known as osmosis [3]. It is caused by a difference in solute concentrations across the membrane, which permits water to pass through while rejecting the majority of the solute ions or particles. Osmosis is used to create the ideal, controlled medicine delivery system. These devices use the osmotic pressure produced by Osmogene as a driving force to release the medicine in a controlled manner. These have a semi-permeable membrane enclosing them with one or more drug delivery channels, allowing the drug to be released gradually as a suspension or solution [4]. The primary component is a drug formulation that comprises a water-swellable polymer and an osmotic agent. The rate at which the osmotic pressure generated by the core's constituent parts and the membrane coating's permeability determine how much water the core can absorb. The drug core swells as it absorbs water, forcing the drug suspension or solution out of the tablet through one or more delivery ports [5,6].
Advantages of Osmotic drug delivery system
Osmotic drug delivery system provides a numerous advantage over other way of drug delivery including:
Disadvantages of Osmotic drug delivery system
Classification of Osmotic drug delivery system
Osmotic drug delivery system is mainly classified in two categories:
Implantable Osmotic drug delivery system
The implantable system consists of three layers: the innermost layer is the drug reservoir, surrounded by an osmotic sleeve containing an osmotic agent, and the outermost layer is a semipermeable membrane. When water passes through the semipermeable membrane and interacts with the osmotic agent, the drug is released from the reservoir [9,10].
Implantable osmotic drug delivery system consists of:
Alzet osmotic pump
It is an implantable osmotic pump used in experimental animals. They are used to deliver homogeneous solutions or suspensions continuously at a controlled rate over an extended period of time. The Alzet pump consists of a hydrocarbon-based thermoplastic elastomer reservoir and a penetrant coating surrounding it. The upper part is a semipermeable membrane made of cellulose ester. The drug is placed in the reservoir and when water enters through the semipermeable membrane and reaches the vicinity of the osmotic agent layer, internal pressure is generated, which releases the drug, thus causing the drug to be released from the device [11].
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Figures Shows Drug Delivery Through Alzet Pump
2.1.2 Rose-Nelson Pump
Rose-Nelson osmotic pump was the first implantable osmotic pump technique developed by Rose and Nelson in 1955. It consists of three parts including a drug chamber, a salt chamber that holds salts and a water chamber. The difference in osmotic pressure across the water chamber and salt chamber affects the flow of water across the membrane [12,13]. The rubber diaphragm separating the salt and drug chambers is supposedly expanded by the water flow, increasing the capacity of the salt chamber; ultimately, the medication is pumped from the apparatus. Basically, this system was developed to deliver drugs into the guts of animals such as sheep and cattle [13].
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2.1.3 Higuchi-Leeper pump
Introduced by Higuchi-Leeper in 1970. In this system, there is no water chamber. The water needed to actuate the device is drawn out from its surroundings. This variant makes it possible to fill the device with a medicine and store it for a long time before using it. It is frequently used in veterinary medicine [14]. An animal's body is fitted with this kind of pump to supply growth hormones or antibiotics. The Higuchi-Leeper pump has a rigid housing reinforced by a semipermeable membrane supported by a perforated frame and a fluid-filled salt chamber. This kind of pump typically has an excess of solid salt. When administered or implanted, the surrounding biological fluid dissolves the MgSO4 and enters the device through a porous, semipermeable membrane. This event creates osmotic pressure inside the device, which forces a movable separator in the direction of the drug chamber to remove the drug out of the device [14,15]
2.1.4 Higuchi-Theeuwes pump
Higuchi and Theeuwes introduced this pump in the early 1970s. The shape of this pump is similar to the Rose-Nelson pump. The medication is put into the apparatus prior to use. This device's semipermeable membrane served as its hard casing [16]. The pumping pressure created inside the device may be tolerated by this membrane because of its strength. The permeability properties of the outer layer and the salt employed in the salt chamber control the drug's release from the device [17].
2.2 Oral osmotic drug delivery system
Advanced drug delivery systems called oral osmotic drug delivery systems (ODDS) are made to regulate how much medication is released into the gastrointestinal (GI) tract. Osmotic pressure is used by these systems to deliver drugs at a regulated and consistent speed, regardless of outside variables such as pH, food consumption, or changes in motility [18].
ODDS function by creating an osmotic gradient between the tablet's core and the external fluid in the gastrointestinal system. The medicine dissolves in water that enters the device through a semipermeable membrane and is forced out through an aperture that has been laser-drilled.
Oral osmotic drug delivery system consists of:
2.2.1 Single layer osmotic systems
Single layer osmotic systems also known as elementary osmotic pump invented by Theuwes in 1974. This system consists of a compressed tablet surrounded by a semipermeable membrane coated with cellulose acetate [19]. The membrane coating is punctured with a tiny hole. The osmotic pressure of the soluble medication within this coated tablet increases when it is exposed to an aqueous environment. A saturated aqueous drug solution forms inside the tablet as water is drawn through the semi-permeable covering. The membrane is not extensible, and the volume increase brought on by water imbibition increases the hydrostatic pressure inside the tablet, which ultimately causes a saturated active agent solution to flow out of the device through a tiny aperture [20]. Drug release is zero-order, which means that it is constant. Drugs with moderate water solubility are considered suitable for this system.
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2.2.2 Push Pull osmotic pump system
It is the modified version of elementary osmotic pump. Push-pull osmotic pumps distribute both highly and weakly water-soluble medications at a steady pace. There are two compartments in this arrangement, and an elastic diaphragm divides them. Upper layer consists of drug in polymeric formulation, osmotic agent and excipients and the lower layer consists of osmotic agent, polymer, colouring agent and other excipients. Tablet core was covered with semipermeable membrane [21]. After coating tiny hole is drilled through the membrane by a mechanical drill on the tablet's drug layer side. When the system is immersed in water, an osmotic agent in both layers draws water into the tablet. An in-situ drug solution is produced when the osmotic attraction in the drug layer pulls water into the compartment. Because the term osmotic agent in the nondrug layers simultaneously draws water into that compartment, the nondrug layer's volumetric expansion forces the drug suspension out of the delivery aperture [22].
2.2.3 Sandwiched osmotic pump system
This system consists of two layers of drug and the polymeric layer is sandwiched between the two-drug layer with two delivery orifices [23]. The middle layer consists of a swelling agent. When the system was placed in an aqueous surrounding, middle layer swells and drug was released from two delivery orifices. This system was mostly suitable for those drugs which cause local irritation of the gastric mucosa [24,25].
2.2.4 Controlled porosity osmotic pump system
It is an osmotic system in which water-soluble pore-forming chemicals integrated into a semipermeable membrane leach to produce the delivery orifices [25]. When the system was exposed to an aqueous surrounding water-soluble particle starts to dissolve and leak out of the system, which results in appearance of micropores in the membrane. Drug release rate from the systems depends on various factors like drug solubility, thickness of coating, osmotic pressure difference across the membrane etc. [18,26].
Osmotic System and their Drawbacks:
EOP- Elementary Osmotic Pump - It consists of only one orifice and the drug is released only in solution form. Suitable only for water-soluble drugs. Drug release follows only zero-order kinetics.
Rose-Nelson Pump: One of the major drawbacks of this pump is that whenever the pump comes into contact with water, its osmotic action begins due to the presence of a semi-permeable membrane. For this reason, the pump is stored empty and in air-tight containers and must be loaded with water before use.
Push–Pull: A push–pull system is better than an EOP system as this system can release drugs both in suspension and solution form. Thus, this system is preferred for highly soluble drugs such as oxybutynin hydrochloride and for very poorly soluble drugs such as glipizide and nifedipine. Meanwhile, the system has a drawback in that a complicated drilling technique is involved in drilling the orifice in the pump.
Push-stick: A push-stick is a longitudinally compressed bilayer tablet system. It consists of a single large orifice and osmotic agents in the push layer. Drug is released from the system as it comes in contact with water and gets moistened, followed by disintegration and then dissolution.
Controlled Porosity and Single Composition Osmotic Tablet (SCOT):
This system consists of a single-layer tablet with no drilled holes; hence, the drug is released from the system through cracks in the form of a wet mass or solution. Compared to other systems, this system significantly reduces gastric irritation. The drug is released from the whole surface of the device (not only from a single orifice). Furthermore, no complex laser drilling, such as that required in a push–pull system, is required since the orifices are formed in situ.
L-OROS: L-OROS is a type of osmotic pump system where the core contains a liquid or semi-solid drug formulation, rather than a solid core like in conventional osmotic tablets (e.g., Elementary Osmotic Pump). These are soft-gel capsules consisting of only one orifice, and the drug is released in liquid form.
Marketed Osmotic-Based Drug Delivery Products:
|
Brand Name |
Generic Name |
Therapeutic Use |
Technology/Remarks |
|
OROS® |
Varies (platform by Alza) |
Multiple (e.g., hypertension, ADHD) |
Proprietary osmotic delivery technology developed by Alza. |
|
Concerta® |
Methylphenidate HCl |
Attention Deficit Hyperactivity Disorder |
OROS® technology; extended release once daily. |
|
Glucotrol XL® |
Glipizide |
Type 2 Diabetes Mellitus |
Gastrointestinal Therapeutic System (GITS). |
|
Procardia XL® |
Nifedipine |
Hypertension, Angina |
GITS technology; 24-hour blood pressure control. |
|
Ditropan XL® |
Oxybutynin chloride |
Overactive bladder |
Osmotic-controlled release oral delivery system. |
|
Covera-HS® |
Verapamil HCl |
Hypertension |
Delayed-release osmotic system for night-time dosing. |
|
Cardura XL® |
Doxazosin mesylate |
Hypertension, BPH |
OROS® push-pull technology. |
|
Alpress LP® |
Prazosin |
Hypertension |
Osmotic pump for extended release. |
|
Lodura® XL |
Loxoprofen sodium |
Anti-inflammatory |
Osmotic extended-release tablet. |
2.3 Specific Types of Osmotic system.
2.3.1 Monolithic Osmotic system
This system involves agent those are water soluble and are dispersed in polymer matrix. Polymers surround the drug by forming capsule. The active chemical compounds draw water into the system when they are brought into touch with aqueous environments, which causes the polymeric capsule encapsulating the medication to burst and release the medicine from the system. The process is carried out at Zero order rate [27].
2.3.2 Colon-Targeted oral osmotic system
A Colon-Targeted Oral Osmotic System is a unique drug delivery device that uses osmotic principles to release medication only in the colon. For the treatment of colonic conditions such as infections, colorectal cancer, and inflammatory bowel disease (IBD), as well as for systemic drug absorption when colonic targeting improves bioavailability, this technique is especially helpful. It could feature a single osmotic pressure agent or a hard gelatin capsule with five or six push-push system osmotic units. When this system is exposed to a stomach environment, the gelatin capsule begins to dissolve. There is an enteric coating to keep stomach contents out of the system [27,28]. The push compartment swells as a result of the fluid entering the system when this coating dissolves in the intestines.
2.3.3 Liquid oral osmotic system
Basically, designed to deliver liquid form of drugs as they provide a high rate and extent of absorption and show extended release of drugs. An osmotic push layer is enclosed by a semi-permeable membrane. This design, which comes in three different versions (hard cap, soft cap, and delayed liquid bolus), is represented by a drug layer [21]. When exposed to an aquatic environment, water imbibition activates the osmotic agent layer. The medicine is forced out of the device's system by hydrostatic pressure as a result of the push layer expanding. This system mostly improves permeability of drugs.
2.3.4 Self-Emulsified osmotic system
These systems are mostly used for delivery of insoluble drug. Here drugs bioavailability was improved by use of self-emulsifying agents which leads to a stable plasma concentration. Some commonly used surfactants include glycerol, oxyethylene glyceryl ricinoleate etc.
Basic components of osmotic pump drug delivery systems:
Factors affecting release of medicament from osmotic drug delivery system:
OSMO Technology Increases Medication Adherence in Patients with Type 2 Diabetes Mellitus:
In Type 2 Diabetes Mellitus (T2DM), long-term management requires strict adherence to oral antidiabetic therapy to maintain glycaemic control and prevent complications. However, non-adherence due to factors like complex dosing schedules, side effects, and inconsistent drug action is a major barrier to effective treatment.
How OSMO Technology Enhances Adherence
Osmotic controlled-release drug delivery systems (OSMO technology) offer a promising solution by improving the convenience, consistency, and tolerability of oral medications. Here’s how:
Once-Daily Dosing: Osmotic systems like Glucotrol XL® (Glipizide) allow for once-daily administration, significantly reducing pill burden. Simplified regimens are proven to increase adherence in chronic diseases like diabetes.
Controlled and Predictable Drug Release: OSMO systems maintain stable plasma drug concentrations throughout the day. Reduces peaks and troughs, which can cause side effects or hypoglycaemic events, leading to better patient confidence and compliance.
Reduced Side Effects: Gradual release minimizes gastrointestinal and systemic side effects, increasing the likelihood of continued use.
Independence from Food and GI Conditions: Drug release in osmotic systems is independent of pH, food, or motility, offering flexibility in dosing times, which suits busy or irregular routines common in diabetic patients.
Improved Quality of Life: Sustained efficacy, reduced side effects, and ease of administration all contribute to a better patient experience, motivating long-term adherence.
Conclusion of OSMO technology:
OSMO technology addresses several barriers to medication adherence in Type 2 diabetes. By enabling once-daily, sustained, and consistent drug delivery, it promotes better patient compliance, reduces the risk of complications, and enhances overall therapeutic outcomes.(29-30)
Metformin Gi Intolerability and Osmo Solution.
Metformin remains the first-line pharmacologic agent for patients with Type 2 Diabetes Mellitus (T2DM) due to its effectiveness, cardiovascular benefits, and cost-efficiency. However, its use is frequently associated with gastrointestinal (GI) adverse effects such as abdominal discomfort, nausea, and diarrhoea, particularly during the initial weeks of therapy. Although strategies like slow dose titration and administering the drug with meals can reduce the incidence of these side effects, GI intolerance continues to be a significant barrier to adherence. In a study conducted by Blonde et al., the frequency of GI adverse events was compared between patients taking metformin extended-release (XR) and those on immediate-release (IR) formulations. The reported incidence rates were as follows:
|
Adverse Event |
Metformin XR (%) |
Metformin IR (%) |
|
Diarrheal |
6.77 |
7.59 |
|
Nausea |
2.26 |
3.80 |
|
Dyspepsia |
1.61 |
1.27 |
|
Abdominal Pain |
1.61 |
0.63 |
|
Constipation |
0.97 |
0.63 |
|
Vomiting |
0.65 |
0.63 |
|
Abdominal Distension |
0.32 |
0.00 |
|
Fecal Abnormality |
0.32 |
0.63 |
|
Blood in Stool |
0.00 |
0.63 |
|
Flatulence |
0.00 |
0.63 |
This comparison highlights that GI side effects persist even with XR formulations, leading to premature discontinuation in some patients—particularly when up-titration is needed for optimal glycaemic control. While extended-release formulations aim to reduce the frequency and severity of GI side effects and improve patient compliance, not all ER technologies are the same. Variations in release mechanisms can significantly influence drug absorption, tolerability, and therapeutic consistency. One promising approach is the osmotic push-pull drug delivery system, a differentiated extended-release technology that offers controlled, predictable, and pH-independent drug release. This system utilizes osmotic pressure to achieve steady plasma concentrations, minimizing fluctuations that could otherwise irritate the GI tract. Compared to traditional ER systems, the push-pull osmotic technology (used in formulations like OROS®) offers several advantages:
Ultimately, the use of osmotic-controlled delivery systems for metformin may help overcome the challenges of GI intolerance, enabling sustained therapy, facilitating achievement of glycaemic targets, and contributing to better long-term outcomes in patients with T2DM. (30-33).
Application of Osmotic drug delivery system
Osmotic drug delivery systems (ODDS) are innovative pharmaceutical technologies designed to control the release of drugs at a steady rate, using osmotic pressure to drive the drug out of a dosage form [11]. These systems have several advantages, including improved bioavailability, reduced side effects, and more consistent therapeutic effects. Below are some key applications of osmotic drug delivery systems:
A. Chronic Disease Management
Osmotic systems are particularly useful in the management of chronic conditions that require continuous drug administration, such as:
Hypertension: Drugs like antihypertensives can be delivered at a controlled rate, reducing the need for frequent dosing and improving patient compliance.
Diabetes: Osmotic systems can be used for controlled release of insulin or other anti-diabetic agents to maintain stable blood glucose levels over time [24].
Pain Management: For conditions like arthritis, osmotic delivery systems can provide a consistent release of analgesics, reducing the peaks and troughs associated with conventional dosing.
B. Controlled Release of Drugs
Osmotic systems can be designed to release drugs at a constant rate, which is beneficial for:
Antibiotics: Controlled release can maintain steady drug concentrations in the bloodstream, improving efficacy and reducing the chances of resistance.
Anti-inflammatory drugs: These drugs can be delivered over an extended period, minimizing side effects such as stomach irritation [26,27].
C. Drugs with Narrow Therapeutic Index
Drugs with a narrow therapeutic index (NTI) require precise control over the dosage to avoid toxicity or ineffectiveness. Osmotic systems can help maintain therapeutic concentrations within the safe range, such as: Anti-cancer agents, Cardiovascular drugs, Anti-epileptic drugs [34].
D. Central Nervous System (CNS) Drugs
Osmotic systems are ideal for CNS drugs that need to be released over a prolonged period, like: Psychiatric medications (e.g., antidepressants, antipsychotics), Anti-seizure medications, Alzheimer’s drugs: Controlled release formulations help maintain a consistent drug level in the brain.
E. Bioavailability Enhancement
In some cases, osmotic systems can improve the bioavailability of drugs that have poor absorption characteristics or undergo extensive first-pass metabolism. This is particularly useful for drugs that require long-term systemic exposure for efficacy [25].
F. Targeted Drug Delivery
Osmotic systems can be modified for targeted delivery, releasing drugs at specific sites in the gastrointestinal tract, or even across the blood-brain barrier, depending on the drug's characteristics [34,35]. This helps in maximizing the therapeutic effect while minimizing systemic side effects.
G. Pediatric and Geriatric Patients
Pediatric patients: Drugs formulated in osmotic systems can reduce the burden of frequent dosing in children, improving compliance and ease of administration. [35].
Geriatric patients: These systems can be particularly beneficial for elderly patients who may have difficulty remembering to take medications or may suffer from conditions requiring complex drug regimens.
H. Non-Oral Drug Delivery
Osmotic drug delivery systems can also be designed for non-oral routes, such as:
Transdermal systems: Using osmotic pressure to drive drugs through the skin for local or systemic effects.
Implantable devices: These systems can provide controlled, long-term drug release for conditions such as cancer, chronic pain, or hormone replacement [36].
I. Hormonal Therapies
Osmotic systems are used in controlled release formulations for hormone replacement therapy (HRT) and contraceptive delivery. For example:
Birth control: Osmotic-controlled release oral delivery systems (OROS) are designed to provide steady hormone release over time, ensuring efficacy with fewer side effects [18].
Estrogen and progesterone therapy: Hormones can be delivered at a steady rate to maintain physiological levels and treat conditions like menopause symptoms or hormone-related cancers [19].
J. Improving Patient Compliance
The convenience of reduced dosing frequency with osmotic systems can significantly improve patient adherence to treatment, leading to better health outcomes, especially in cases where treatment requires long-term therapy [19].
CONCLUSION:
An important development in the treatment of diabetes is Osmotic Controlled Drug Delivery Systems (OSMO) technology, which provides a dependable and patient-centred method of oral medication administration. Many of the issues with conventional antidiabetic treatments, including frequent dosage, adverse effects, and irregular plasma drug levels, are resolved by OSMO devices, which offer controlled, prolonged, and predictable drug release. With once-daily dose, reduced gastrointestinal side effects, and independence from diet and gastrointestinal fluctuation, this technology improves patient adherence. These factors are particularly crucial for the long-term management of Type 2 Diabetes Mellitus (T2DM). Its use to enhance the tolerability of first-line medications, such as metformin, further demonstrates its clinical significance and potential to maximize therapeutic results. All things considered, OSMO technology is a promising tactic in the continuous endeavour to enhance chronic disease management since it not only increases clinical efficacy and treatment compliance but also enhances the quality of life for diabetes patients.
REFERENCES
Tapas Kumar Mohapatra*, Akankshya Raul, Soumyashree Dehury, Rajesh Kumar Pothal, Advancements in Osmotic Controlled Drug Delivery Systems and Their Role in Diabetes Management, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 1410-1422 https://doi.org/10.5281/zenodo.15379161
10.5281/zenodo.15379161
