Published on July 15, 2014
RECENT ADVANCES IN FLOATING DRUG DELIVERY SYSTEM : RECENT ADVANCES IN FLOATING DRUG DELIVERY SYSTEM INTRODUCTION : INTRODUCTION Approaches To Floating Dosage Forms Mechanism of floating drug delivery systems Drugs Used In the Formulations of Stomach Advantages of Floating Drug Delivery Limitations/Disadvantages In vitro and In vivo Evaluation Parameters of Stomach Specific FDDS PowerPoint Presentation: Recent Advances in Stomach Specific Floating Dosage Forms Future potential References INTRODUCTION : INTRODUCTION Several difficulties are faced in designing controlled release systems for better absorption and enhanced bioavailability. One of such difficulties is the inability to confine the dosage form in the desired area of the gastrointestinal tract. Drug absorption from the gastrointestinal tract is a complex procedure and is subject to many variables. It is widely acknowledged that the extent of gastrointestinal tract drug absorption is related to contact time with the small intestinal mucosa.Gastroretentive systems can remain in the gastric region for several hours and hence significantly Prolong the gastric residence time of drugs PowerPoint Presentation: Prolonged gastric retention improves bioavailability, reduces drug waste, and improves solubility for drugs that are less soluble in a high pH environment. To formulate a successful stomach specific or gastro retentive drug delivery system, several Techniques are currently used such as hydro dynamically balanced systems (HBS) /floating drug delivery system3, low-density system, raft systems incorporating alginate gels, Bioadhesive or mucoadhesive systems, high density systems super porous hydro gels and Magnetic systems. Approaches To Floating Dosage Forms : Approaches To Floating Dosage Form s The following approaches have been used: A. Single Unit Floating Dosage Systems B. Multiple Unit Floating Dosage Systems C . Raft Forming System A. Single unit floating dosage : A. Single unit floating dosage a) Effervescent Systems (Gas generating systems ) b) Non-effervescent Systems B. Multiple unit floating dosage : B. Multiple unit floating dosage a) Non-effervescent Systems b) Effervescent Systems (Gas-generating Systems ) c) Hollow Microspheres C. Raft forming systems : C. Raft forming systems Raft forming systems have received much attention for the delivery of antacids and drug delivery for gastrointestinal infections and disorders. The mechanism involved in the raft formation includes the formation of viscous cohesive gel in contact with gastric fluids, wherein each portion of the liquid swells forming a continuous layer called a raft. Mechanism of floating drug delivery systems : Mechanism of floating drug delivery systems While the system is floating on the gastric the drug is released slowly at the desired rate from the system. After release of drug, the residual system is emptied from the stomach besides a minimal gastric content needed to allow the proper achievement of the buoyancy retention principle, a minimal level of floating force (F) is also required to keep the dosage form reliably buoyant on the surface of the meal. PowerPoint Presentation: To measure the floating force kinetics, a novel apparatus for determination of resultant weight has been in the literature. the apparatus operates by measuring continuously the force equivalent to f (as a function of time) that is required to main submerged object. The object floats better if F is on the higher positive side (Fig. 1(b)). PowerPoint Presentation: This apparatus helps in optimizing FDDS with respect to stability and durability of floating forces produced in order to prevent the drawbacks of unforeseeable intragastric buoyancy capability variations. F = F buoyancy - F gravity = (Df - Ds) gv--- Where, F= total vertical force, Df = fluid density, Ds = object density, v = volume and g = acceleration due to gravity. Approaches to design : Approaches to design Drugs Used In the Formulations of Stomach : : Drugs Used In the Formulations of Stomach : Floating microspheres : Aspirin, Griseofulvin, P-nitro aniline, Ibuprofen, Ketoprofen, Piroxicam, Verapamil, Cholestyramine, Theophylline, Nifedipine, Nicardipine, Dipyridamol, Tranilast . Floating gran ules: Diclofenac sodium, Indomethacin and Prednisolone. Films : Cinnarizine and Albendazole. PowerPoint Presentation: Floating tablets and pills: , Verapamil hydrochloride, Acetaminophen, Acetylsalicylic acid, Ampicillin, Amoxycillintrihydrate, Atenolol, Fluorouracil, Cephalexin, Cefuroxime auxetil, Isosorbide mononitrate, p aminobenzoic acid, Piretanide, Theophylline Chlorpheniramine maleate, Aspirin, Calcium Carbonate, Fluorouracil, Prednisolone, Sotalol, pentoxyfilline and Diltiazem HCl . PowerPoint Presentation: Floating Capsules : Chlordiazepoxide hydrogen chloride, Diazepam, Furosemide, Misoprostol, L-Dopa, Benserazide, Ursodeoxycholic acid and Pepstatin and Propranolol Advantages of Floating Drug Delivery: : Advantages of Floating Drug Delivery : 1. Enhanced bioavailability 2. Enhanced first-pass biotransformation 3. Sustained drug delivery/reduced frequency of dosing 4. Targeted therapy for local ailments in the upper GIT 5. Reduced fluctuations of drug concentration PowerPoint Presentation: 6. Improved receptor activation selectivity 7. Reduced counter-activity of the body 8. Extended time over critical (effective) concentration 9. Minimized adverse activity at the colon 10. Site specific drug delivery Limitations/Disadvantages :· : Limitations/Disadvantages :· These systems require a high level of fluid in the stomach for drug delivery tom float and work efficiently-coat, water. · Not suitable for drugs that have solubility or stability problem in GIT. · Drugs such as Nifedipine which is well absorbed along the entire GIT and which undergoes first pass metabolism, may not be desirable. · Drugs which are irritant to Gastric mucosa are also not desirable or suitab le. PowerPoint Presentation: · The drug substances that are unstable in the acidic environment of the stomach are not suitable candidates to be incorporated in the systems. · The dosage form should be administered with a full glass of water (200-250 ml). · These systems do not offer significant advantages over the conventional dosage forms for drugs, which are absorbed throughout the gastrointestinal tract. In vitro and In vivo Evaluation Parameters of Stomach Specific FDDS : In vitro and In vivo Evaluation Parameters of Stomach Specific FDDS 1) Measurement of buoyancy capabilities of the FDDS: 2) Floating time 3) Drug release 4) Content uniformity, Hardness, Friability (Tablets) 5) Drug loading, drug entrapment efficiency, particle size analysis, surface characterization (for floating microspheres and beads) PowerPoint Presentation: 6) Resultant weight 7) X-Ray/Gamma Scintigraphy 8) Pharmacokinetic studies 9) Specific Gravity Recent Advances in Stomach Specific Floating Dosage Forms : Recent Advances in Stomach Specific Floating Dosage Forms Ninan Ma et al developed a type of multi-unit floating alginate (Alg) microspheres by the ionotropic gelation method with calcium carbonate (CaCO3) being used as gas-forming agent. Strübing et al investigated the mechanism of floating and drug release behavior of poly (vinyl acetate)-based floating tablets with membrane controlled drug delivery . PowerPoint Presentation: Jang et al has prepared a gastro retentive drug delivery system of DA-6034, a new synthetic flavonoid derivative, for the treatment of gastritis was developed by using effervescent floating matrix system (EFMS). The therapeutic limitations of DA-6034 caused by its low solubility in acidic conditions were overcome by using the EFMS PowerPoint Presentation: Sungthongjeen et al have prepared a floating multilayer coated tablets based on gas formation. The system consists of a drug-containing core tablet coated with a protective layer ( hydroxypropyl methylcellulose ), a gas forming layer (sodium bicarbonate) and a gas-entrapped membrane, respectively . PowerPoint Presentation: Rajnikanth and Mishra have developed a floating in-situ gelling system of Clarithromycin (FIGC) using gellan as gelling polymer and calcium carbonate as floating agent for potentially treating gastric ulcers, associated with Helicobacter pylori. The addition of Sucralfate to the formulation significantly suppressed the degradation of Clarithromycin at low pH . PowerPoint Presentation: Zhihong Zhang et al designed a novel system, which combined the osmotic pump controlled release system and the floating system; matrix tablets (MT) were prepared for comparison. Dipyridamole was chosen as the model drug. The effects of pH, temperature and hydrodynamic conditions on drug release and the floating behavior of floating osmotic pump system (FOP) was investi gated. PowerPoint Presentation: Shalesh T. Prajapati et al developed an optimized gastric floating drug delivery system (GFDDS) containing Domperidone as a model drug. Box-Behnken design was employed in formulating the GFDDS with three polymers: hydroxypropyl methylcellulose K4M (HPMC K4M) (X1), Carbopol 934P (X2) and sodium alginate (X3), as independent variables. Floating lag time (FLT), total floating time (TFT), time required to release 50% of the drug ( t 50) and diffusion exponent (n) were selected as dependent variables. Future Potential : Future Potential Floating dosage form offers various future potential as evident from several recent publications. Among the recently used clinical drugs several narrow absorption window drugs may benefit from compounding into a FDDS. Replacing parenteral administration of drugs to oral pharmacotherapy would substantially improve treatment. It may be believed that it can be possible with FDDS. Drugs that have poor bio-availability because of their limited absorption to the upper gastrointestinal tract can be delivered efficiently into FDDS. Thereby maximizing their absorption and improving their absolute bioavailability. PowerPoint Presentation: The floating concept can also be utilized in the development of various anti-reflux formulations. Developing a controlled release system for the drugs, which are potential to treat the Parkinson’s disease, is also an important area of consideration. Combination therapy to treat H.Pylori infection in a single FDDS needs to be developed. The study of the effect of various geometric shapes in a more excessive manner than previous studies on gastroretentivity needs to be developed. The investigations can be concentrated on the concept of design of novel polymers according to clinical and pharmaceutical need. REFERENCES : REFERENCES Asian Journal of Pharmacy and Life Science  Shivkumar HG; Vishakante Gwdaand D; Pramod Kumar TM. Indian J Pharm Educ, 2004,38(4 ), 172-179.  Shah SH; Patel JK; Patel NV. Int J Pharm Tech Res , 2009, 1(3), 623-633.