You are hereA SHORT REVIEW ON STOMACH SPECIFIC DRUG DELIVERY SYSTEM
A SHORT REVIEW ON STOMACH SPECIFIC DRUG DELIVERY SYSTEM
Evaluation parameters of stomach specific FDDS
However, it has to be pointed out that good in vitro floating behaviour alone is not sufficient proof for efficient gastric retention in vivo. The effects of the simultaneous presence of food and of the complexmotility of the stomach are difficult to estimate. Obviously, only in vivo studies can provide definite proof that prolonged gastric residence is obtained.
1) Measurement of buoyancy capabilities of the FDDS.82The floating behaviour was evaluated with resultant weight measurements. The experiment was carried out in two different media, deionised water and simulated meal, in order to monitor possible difference. The results showed that higher molecular weight polymers with slower rate of hydration had enhanced floating behaviour and it was observed more in simulated meal medium compared to deionised water.
2) Floating time and dissolution: The test for floating time measurement is usually performed in stimulated gastric fluid or 0.1 mole.lit-1 HCl maintained at 370o C. It is determined by using USP dissolution apparatus containing 900 ml of 0.1 mole.lit-1 HCl as the dissolution medium at 370o C. The time taken by the dosage form to float is termed as floating lag time and the time for which the dosage form floats is termed as the floating or flotation time.83
Recently Gohel et al 84 proposed a more relevant in vitro dissolution method to evaluate a floating drug delivery system (for tablet dosage form). A 100-mL glass beaker was modified by adding a side arm at the bottom of the beaker so that the beaker can hold 70 ml of 0.1 mole.lit-1 HCl dissolution medium and allow collection of samples. A burette was mounted above the beaker to deliver the dissolution medium at a flow rate of 2 ml/min to mimic gastric acid secretion rate. The performance of the modified dissolution apparatus was compared with USP dissolution.
Apparatus 2 (Paddle) The problem of adherence of the tablet to the shaft of the paddle was observed with the USP dissolution apparatus. The tablet did not stickto the agitating device in the proposed dissolution method. The drug release followed zero-order kinetics in the proposed method. Similarity of dissolution curves was observed between the USP method and the proposed method at 10% differencelevel (f2=57). The proposed test may show good in vitro-in vivo correlation since an attempt is made to mimic the in vivo conditions such as gastric volume, gastric emptying, and gastric acid secretion rate.
3) Drug release: Dissolution tests are performed using the dissolution apparatus. Samples are withdrawn periodically from the dissolution medium with replacement and then analyzed for their drug content after an appropriate dilution.
4) Content uniformity, Hardness, Friability (Tablets).
5) Drug loading, drug entrapment efficiency, particle size analysis, surface characterization(for floating microspheres and beads) Drug loading is assessed by crushing accurately weighed sample of beads or microspheres in a mortar and added to the appropriate dissolution medium which is then centrifuged, filtered and analyzed by various analytical methods like spectrophotometry. The percentage drug loading is calculated by dividing the amount of drug in the sample by the weight total beads or microspheres. The particle size and the size distribution of beads or microspheres are determined in the dry state using the optical microscopy method. The external and cross-sectional morphology (surface characterization) is done by scanning electron microscope (SEM).85
6) X-Ray/Gamma Scintigraphy:X-Ray/Gamma Scintigraphy is a very popular evaluation parameter for floating dosage form now a day.86 It helps to locate dosage form in the GIT and by which one can predict and correlate the gastric emptying time and the passage of dosage form in the GIT. Here the inclusion of a radio-opaque material into a solid dosage form enables it to be visualized by X- rays. Similarly, the inclusion of a γ-emitting radionuclide in a formulation allows indirect external observation using a γ-camera or scintiscanner.87 In case of γ-scintigraphy, the γ-rays emitted by the radionuclide are focused on a camera, which helps to monitor the location of the dosage form in the GI tract.88
7) Pharmacokinetic studies:Pharmacokinetic studies are the integral part of the in vivo studies and several works has been on that. Sawicki89 studied the pharmacokinetics of verapamil, from the floating pellets containing drug, filled into a capsule, and compared with the conventional verapamil tablets of similar dose (40 mg). The tmax and AUC (0-infinity) values (3.75 h and 364.65ng.ml-1h respectively) for floating pellets were comparatively higher than those obtained for the conventional verapamil tablets (tmax value 1.21 h, and AUC value 224.22ng.ml-1h). No much difference was found between the Cmax values of both the formulations, suggesting the improved bioavailability of the floating pellets compared to the conventional tablets. An improvement in bioavailability has also been observed with piroxicam in hollow polycarbonate microspheres administered in rabbits. The microspheres showed about 1.4 times more bioavailability, and the elimination half-life was increased by about three times than the free drug.
Recent advances in stomach specific floating dosage forms
Ninan Ma et al 90 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. Attempts were made to enhance the drug encapsulation efficiency and delay the drug release by adding chitosan (Cs) into the gelation medium and by coating with Eudragit, respectively. The gastrointestinal transit of optimized floating sustained-release microspheres was compared with that of the non-floating system manufactured from identical material using the technique of gamma-scintigraphy in healthy human volunteers. It was found that the drug encapsulation efficiency of Cs–Alg microspheres was much higher than that of the Ca–Alg microspheres, andcoating the microspheres with Eudragit RS could extend the drug release significantly. Both uncoating and coating microspheres were able to continuously float over the simulated gastric fluid (SGF) for 24 h in vitro. Prolonged gastricretention time (GRT) of over 5 h was achieved in the volunteer for the optimized coating floating microspheres (FM). In contrast, non-floating system (NFM) could be emptied within 2.5 h.
Strübing et al 91 investigated the mechanism of floating and drug release behaviour of poly (vinyl acetate)-based floating tablets with membrane controlled drug delivery. Propranolol HCl containing tablets with Kollidon® SR as an excipient for direct compression and different Kollicoat® SR 30 D/Kollicoat® IR coats varying from 10 to 20 mg polymer/cm2were investigated regarding drug release in 0.1 mole. lit-1 HCl. Furthermore, the onset of floating, the floating duration and the floating strength of the device were determined. In addition, benchtop MRI studies of selected samples were performed. Coated tablets with 10 mg polymer/cm2SR/IR, 8.5:1.5 coat exhibited the shortest lag times prior to drug release and floating onset, the fastest increase in and highest maximum values of floating strength. The drug release was delayed efficiently within a time interval of 24 h by showing linear drug release characteristics.
Jang et al 92 has prepared a gastroretentive drug delivery system of DA-6034, a new synthetic flavonoidderivative, 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, which was designed to cause tablets to float in gastric fluid and release the drug continuously. The release of DA-6034 from tablets in acidic media was significantly improved by using EFMS, which is attributed to the effect of the solubilizers and the alkalizing agent such as sodium bicarbonate used as gas generating agent. DA-6034 EFMS tablets showed enhanced gastroprotective effects in gastric ulcer-induced beagle dogs, indicating the therapeutic potential of EFMS tablets for the treatment of gastritis.
Sungthongjeen et al93 have prepared a floating multi-layer 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. Eudragit® RL 30D was chosen as a gas-entrapped membrane due to its high flexibility and high water permeability. The obtained tablets enabled to float due to the CO2-gas formation and the gas entrapment by polymeric membrane. The effect of formulation variables on floating properties and drug release was investigated. The floating tablets using direct-compressed cores had shorter time to float and faster drug release than those using wet-granulated cores. The increased amount of a gas forming agent did not affect time to float but increased the drug release fromthe floating tablets while increasing coating level of gas-entrapped membrane increased time to float (more than 8 hours) and slightly retarded but sustained drug release.
Rajnikanth and Mishra 94 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. Gellan based FIGC was prepared by dissolving varying concentrations of gellan in deionized water to which varying concentrations of drug and sucralfate were dispersed well. The addition of sucralfate to the formulation significantly suppressed the degradation of clarithromycin at low pH. FIGC showed a significant anti-H. pylori effect than that of clarithromycin suspension. The in situ gel formulation with sucralfate cleared H. pylori more effectively than that of formulation without sucralfate. In addition, the required amount of clarithromycin for eradication of H. pylori was found to be less from FIGC than from the corresponding clarithromycin suspension. It was concluded that prolonged gastrointestinal residence time and enhanced clarithromycin stability resulting from the floating in situ gel of clarithromycin might contribute better for complete clearance of H. pylori.
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