12-08-2014, 03:52 PM
1.1 Oral Dispersible Tablet
Oral Dispersible Tablet.docx (Size: 1.7 MB / Downloads: 10)
INTRODUCTION
An ideal dosage regimen in the drug therapy of any disease is the one, which immediately attains the desire therapeutics concentration of drug in plasma (or at the site of action) and maintains it constant for the entire duration of treatment1.
Drugs are frequently taken by oral administration. Although a few drugs taken orally are intended to be dissolved within the mouth, majority of drugs taken orally are swallowed. Compared with alternate routes, the oral route of drug administration is the most popular and has been successfully used for conventional delivery of drug. It is considered as most natural, convenient means of administering
drugs2.
One important drawback of these dosage forms was many patients have difficulty in swallowing tablets and hard gelatin capsules and consequently do not take medications as prescribed. It is estimated that 50% of the population is affected by this problem, which results in a high incidence of noncompliance and ineffective therapy3. It has been reported that dysphagia (difficulty in swallowing) is common among all age groups and more specific with pediatric, geriatric population along with institutionalized patients and patients with nausea4.
This problem can be resolved by the creation of rapidly dispersing or dissolving oral forms, which do not require water to aid swallowing. The dosage forms are placed in the mouth, allowed to disperse or dissolve in the saliva, and then are swallowed in the normal way3.
1.6.2 Palatability
Oral dispersible tablets dissolve or disintegrate near the taste buds. A pleasant taste inside the mouth becomes critical for patient acceptance. Unless the drug is tasteless or does not have an undesirable taste, taste-masking techniques should be used. An ideal taste-masking technique should provide good mouth feel and should be compatible with ODT formulations. The amount of taste masking material should be as low as possible to reduce the tablet size.
1.6.3 Tablet Strength and Porosity
In order to disintegrate the oral dispersible tablet in the oral cavity, the tablet structure should have a highly porous network and should use low compression force, which makes the tablets friable or brittle, which is difficult to handle. Because the strength of a tablet is related to compression pressure, it is important to find the porosity that allows fast water absorption while maintaining high mechanical strength.
1.8.3 Durasolve Technology
DuraSolve is Cima's second-generation mouth-dissolving/disintegrating tablet formulation. Produced in a fashion similar to OraSolve, DuraSolve has much higher mechanical strength than its predecessor due to the use of higher compaction pressures during tableting. DuraSolve tablets are prepared by using conventional tabletting equipment and have good rigidity (friability less than that 2%). The DuraSolve product is thus produced in a mouther and more cost-effective manner. DuraSolve is so durable that it can be packaged in traditional blister packaging, pouches or vials. One disadvantage of DuraSolve is that the technology is not compatible with larger doses of active ingredients, because the formulation is subjected to such high pressures on compaction. Example: risperidone
1.8.9 Nanocrystal Technology
For mouth dissolving tablets, Elan's proprietary NanoCrystal technology can enable formulation and improve compound activity and final product characteristics. Decreasing particle size increases the surface area, which leads to an increase in dissolution rate. This can be accomplished predictably and efficiently using NanoCrystal technology. NanoCrystal particles are small particles of drug substance, typically less than 1000 nm in diameter, which are produced by milling the drug substance using a proprietary wet milling technique. NanoCrystal colloidal dispersions of drug substance are combined with water-soluble ingredients, filled into blisters, and lyophilized. The resultant wafers are remarkably robust, yet dissolve in very small quantities of water in seconds. Example: rapamycin
Mechanism of Action
Tramadol and its O-desmethyl metabolite (M1) are selective, weak OP3-receptor agonists. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. The analgesic properties of Tramadol can be attributed to norepinephrine and serotonin reuptake blockade in the CNS, which inhibits pain transmission in the spinal cord. The (+) enantiomer has higher affinity for the OP3 receptor and preferentially inhibits serotonin uptake and enhances serotonin release. The (-) enantiomer preferentially inhibits norepinephrine reuptake by stimulating alpha (2)-adrenergic receptors.
Conclusion
The formulation containing 50mg of Tramadol hydrochloride was prepared as orally dispersible tablet. These techniques are particularly useful for geriatrics and pediatrics can be taken without the aid of water.
The optimized formulation have consistent release profile to provide the disintegration with in one minute by Crospovidone (F3).The short term stability study also indicates no change in the physical characteristic of drug content.
The comparision of pharmacokinetic parameters between the ODTs Tramadol HCl and conventional tablet, showed no major changes in the pharmacokinetic parameters. Hence, it can be concluded that the ODTs of Tramadol HCl was successfully developed and evaluated.