DESIGN, OPTIMIZATION, AND EVALUATION OF RAFT FORMING GASTRO RETENTIVE DRUG DELIVERY SYSTEM OF LAFUTIDINE USINGBOX–BEHNKEN DESIGN

Objective: The current research was aimed to formulate and evaluate raft forming gastro retentive floating drug delivery systems of Lafutidine for improving gastric residence time and sustained drug release for an extended time. Methods: Using Box–Behnken experimental design 17 formulations of lafutidine GRDDS were designed and evaluated for various parameters like physical appearance, pH, In vitro gelling study, in vitro buoyancy study, measurement of viscosity, density measurement, gel strength, drug content, acid neutralization capacity, the profile of neutralization, in vitro dissolution, release kinetic and stability studies. Results: All the evaluations were performed and observed that the values were within range, and the buoyancy lag time ranged within 14.76 to 25.84 sec and the formulations remained buoyant for more than 8h with the gelling time of 12h, the drug content was ranging from 98.96 to 99.55 %, and in vitro release was 86.86 to 99.34% by the end of 12h. The release kinetics followed zero-order with Higuchi’s model that indicating that drug release was found to be followed by the matrix diffusion process. Conclusion: Out of all formulations F3 was the optimized formulation and it was further characterized for FTIR, DSC, and stability studies, which exposed that there were no interactions amongst drug and excipients and no major change in the formulation and found to be stable.

Ambroxol Hydrochloride Loaded Gastro-Retentive Nanosuspension Gels Potentiate Anticancer Activity in Lung Cancer (A549) Cells

This study aimed to develop gastro-retentive sustained-release ambroxol (ABX) nanosuspensions utilizing ambroxol-kappa-carrageenan (ABX-CRGK) complexation formulations. The complex was characterized by differential scanning calorimetry, powder x-ray diffractometer, and scanning electron microscopy. The prepared co-precipitate complex was used for the development of the sustained-release formulation to overcome the high metabolic and poor solubility problems associated with ABX. Furthermore, the co-precipitate complex was formulated as a suspension in an aqueous floating gel-forming vehicle of sodium alginate with chitosan, which might be beneficial for targeting the stomach as a good absorption site for ABX. The suspension exhibited rapid floating gel behaviour for more than 8 h, thus confirming the gastro-retentive effects. Particle size analysis revealed that the optimum nanosuspension (ABX-NS) had a mean particle size of 332.3 nm. Afterward, the ABX released by the nanoparticles would be distributed to the pulmonary tissue as previously described. Based on extensive pulmonary distribution, the developed nanosuspension-released ABX nanoparticles showed significant cytotoxic enhancement compared to free ABX in A549 lung cancer cells. However, a significant loss of mitochondrial membrane potential (MMP) also occurred. The level of caspase-3 was the highest in the ABX-NS-released particle-treated samples, with a value of 416.6 ± 9.11 pg/mL. Meanwhile, the levels of nuclear factor kappa beta, interleukins 6 and 1 beta, and tumour necrosis alpha (NF-kB, IL-6, IL-1β, and TNF-α, respectively) were lower for ABX-NS compared to free ABX (p < 0.05). In caspase-3, Bax, and p53, levels significantly increased in the presence of ABX-NS compared to free ABX. Overall, ABX-NS produced an enhancement of the anticancer effects of ABX on the A549 cells, and the developed sustained-release gel was successful in providing a gastro-retentive effect.

Gastro-retentive drug delivery system: A better approach of drug delivery system

The oral route is the best and most popular route for the administration of drugs in the systemic circulation. There are number of drugs which are given through the oral route. Gastro-retentive drug delivery system is very important system for the drug delivery system. The gastro-retentive drugs prolonged the drug time in the git and also improve their their bioavailability. These are widely used for site specific for the treatment of git disorders and diseases. There are number of approaches for gastro retentive drug delivery system such as floating system, mucoadhesive system, swelling system, high density system etc. In this review we discussed about approaches and various perspectives of gastro retentive drug delivery system.

Pharmacoscintigraphic evaluation and antidiabetic efficacy of gliclazide-loaded 99mTc-labelled mucoadhesive microspheres

Background The current study was carried out to evaluate the possible application of Musa balbisiana starch in formulation of mucoadhesive microsphere for oral delivery of gliclazide (GLZ). The study objective was to improve the oral bioavailability along with prolongation of its duration of action for a better glycaemic control. Ionic gelation technique was employed in formulating the dosage form. Optimization of the batches was carried out by response surface methodology using 32 full factorial designs. The microsphere prepared was characterized for several parameters along with its in vitro release study. The gastrointestinal transit of the optimized batch of prepared microspheres after oral administration was studied in rabbits by using the gamma scintigraphy technique utilizing 99mTc as the labelling agent in the presence of stannous chloride. Also, the optimized batch was studied for its pharmacokinetic parameters. Moreover, the antidiabetic efficacy of the prepared microsphere was evaluated in rats by using the streptozotocin (STZ)-induced diabetic model. Results The factorial design experiment resulted in an optimum formulation coded as F8. The compatible nature of the drug and excipient was revealed from FTIR, DSC and IST studies. The scanning electron micrographs also showed the occurrence of spherical microspheres having a smooth surface. The in vitro release study provided an evidence of an initial burst effect that was followed by a prolong release phase. The pharmacokinetic parameters justified the ability of the prepared dosage form in sustaining the drug release with a 2.7-fold enhancement in drug bioavailability. The images obtained during the gamma scintigraphy study suggested the gastro-retentive nature of the dosage form with the gastro-retentive ability for more than 4 h. Also, the pharmacodynamics study carried out in diabetic rat model confirmed about the better efficacy of the dosage form in lowering the elevated blood glucose level. Conclusion The overall study data provide valuable information about the potential of this banana starch in formulation of a mucoadhesive dosage form that can be used for enhancement of bioavailability of drug-like gliclazide which in turn can provide a beneficial effect in the management of diabetes.

Development and Evaluation of Gastro Retentive Floating Drug Delivery System of Ondansetron Hydrochloride

The Aim of the present study was to develop & evaluate Gastro-retentive floating Tablet of Ondansetron hydrochloride. The Objective was to calibrate and validate the UV- spectroscopy analytical method and to prepare and optimize the GR Floating tablets of Ondansetron hydrochloride in terms of dissolution release profile. The FDDS of the drug can minimize the fluctuation of drug plasma levels and result to associated adverse reactions, dosing frequency, and improved patient compliance. Conventionally, Ondansetron hydrochloride is taken up 2-3 times daily in the treatment of nausea and vomiting. Gastro retentive floating tablet of Ondansetron hydrochloride is better suited for treatment of postoperative nausea vomiting. In the present study, nine Gastro retentive Floating tablet formulations (F1, F2.....F9) of Ondansetron hydrochloride were prepared by the method of direct compression and polymers HPMC K15 were used and Guargum and Chitosan, in different quantity to normalise their effect on the’ release profile of drug . Target release profile was >80% release of drug in 12 hours. Tablets were evaluated for various parameters namely: thickness, weight variation’, friability, hardness, assay, in-vitro buoyancy study & drug release. Formulation F8 containing Chitosan (26.66% w/w), Guargum (26.66% w/w) and Sod. Carbonate (25.83% w/w) had the desirable release profile. Keywords: Ondansetron hydrochloride; Gastro retentive floating tablet, Chitosan, Guar gum, Drug release

Floating Drug Delivery System an Aid to Enhance Dissolution Profile of Gastric

With the GRDDS, the dose shape remains controllably in the stomach after oral administration, so that the medication may be continually delivered to its absorption receptors in the intestinal tract. The medicine is delivering in a controlled and extended way. Gastro-retentive dose in the stomach area may last for another few hours and substantially lengthen the gastric residence period of the medicines. While the bulk density in the system for the supply of floating medicines (FDDS) exceeds the gastric fluids, it remains for an extended duration in the stomach without altering the rate of decomposition. The medication distributes gradually as the system floats on the stomach juice. As a consequence, stomach residency takes longer and plasma concentrations are well monitored. The therapy of peptic ulcer illness might be beneficial for local activity in the upper portion of the intestine, i.e., a longer stomach residency. In addition, medicines rapidly absorbed in the GI tract will increase bioavailability through delayed stomach release. The regulated gastric retention of solid dose forms can also be accomplished by the simultaneous administration of pharmacological agents, or by sedimentation, flotation processes, muco-adhesion, expansion, changed shape systems, by delaying the stomach emptying. Keywords: Gastro-retentive drug delivery system, Floating drug delivery system, Muco-adhesion, Bioavailability.

Floating microspheres of Miglitol as gastro retentive drug delivery system: 32 full factorial design and in vitro evaluation

Background: The goal of this study was to develop a gastro retentive floating drug delivery system that would improve site specific activity, patient compliance and therapeutic efficacy.Methodology: Floating microspheres of Miglitol were formulated by double emulsion method using ethyl cellulose and eudragit E100 different weight ratio and PVA as an emulsifier. It has been prepared with respect quantity of polymer concentration and stirring speed to evaluate for % buoyancy, drug entrapment efficiency, particle size drug release rate. Result: The percent of buoyancy, drug entrapment efficiency, particle size, and percentage yield were increased with increase the polymer mixture concentration. Among all formulation batches, F6 showed acceptable results drug entrapment efficiency (86.57%) and buoyancy (94.25%). F10 formulation was prepared to check the predicted and actual factors and compared with optimized formulation F6. The drug release was increased as the polymer concentration was decrease. The kinetic model zero order had the highest regression coefficient value, it was described as a sustained release dosage form. According to ICH guideline accelerated stability studies of F6 and F10 formulations were conducted for 90 days. After 90 days buoyancy and in vitro drug release was performed and the results were F6 and F10 buoyancy was found to be 88.21%, 87.22% and in vitro drug release was found to be 62.87%, 63.51%. Conclusion: The present study, showed compatibility of drug with polymers by FTIR in formulation. Floating microsphere of Miglitol was prepared by double emulsion technique. The F6 Miglitol floating microsphere was optimized formulation demonstrated with excellent drug entrapment performance (86.57%), good floating behaviour (94.25%), and the largest particle size (670µm). The present study concludes that floating based gastro retentive delivery system of Miglitol microspheres has a safe and effective drug delivery system with increased therapeutic efficacy and a longer duration of action.