Ondansetron Hydrochloride Research Articles

Central Composite Designed Fast Dissolving Tablets for Improved Solubility of the Loaded Drug Ondansetron Hydrochloride.

Ondansetron tablets that are directly compressed using crospovidone and croscarmellose as a synthetic super disintegrant are the subject of this investigation. A central composite, response surface, randomly quadratic, nonblock (version 13.0.9.0) 32 factorial design is used to optimize the formulation (two-factor three-level). To make things even more complicated, nine different formulation batches (designated as F1–F9) were created. There were three levels of crospovidone and croscarmellose (+1, 0, -1). In addition to that, pre- and postcompressional parameters were evaluated, and all evaluated parameters were found to be within acceptable range. Among all postcompressional parameter dispersion and disintegration time, in vitro drug release experiments (to quantify the amount of medication released from the tablet) and their percentage prediction error were shown to have a significant influence on three dependent variables. Various pre- and postcompression characteristics of each active component were tested in vitro. Bulk density, tap density, angle of repose, Carr's index, and the Hausner ratio were all included in this analysis, as were many others. This tablet's hardness and friability were also assessed along with its dimension and weight variations. Additional stability studies may be conducted using the best batch of the product. For this study, we utilised the Design-Expert software to select the formulation F6, which had dispersion times of 17.67 ± 0.03 seconds, disintegration times of 120.12 ± 0.55 seconds, and percentage drug release measurements of 99.25 ± 0.36 within 30 minutes. Predicted values and experimental data had a strong correlation. Fast dissolving pills of ondansetron hydrochloride may be created by compressing the tablets directly.

Development and characterization of polymeric nanoparticles containing ondansetron hydrochloride as a hydrophilic drug

The encapsulation of hydrophilic drugs is still a challenge due to their tendency to leak into the outer aqueous phase. The aim of the study is to develop and evaluate Ondansetron HCl (OND) loaded controlled release polymeric nanoparticles with high encapsulation efficiency (EE). Polymeric nanoparticles (PNPs) were prepared with two different types of polycaprolactone and five different types of poly (d, l-lactide-co-glycolide) (PLGA) by the double emulsion solvent evaporation method. The effects of formulation variables on the particle size, zeta potential, encapsulation efficiency, and drug release of OND loaded PNPs were investigated. The particle size, PDI, and zeta potential of the optimum formulation were 342.5 ± 6.7 nm, 0.240 ± 0.020, and −20.1 ± 0.51 mV, respectively, whereas the encapsulation efficiency was 46.8 ± 2.78%. The optimum formulation was pegylated to prolong the residence time in circulation. Transmission electron microscopy (TEM) images confirmed the spherical shape of nanoparticles. Pegylated formulation had 47.76 ± 1.69% encapsulation efficiency and sustained release profile (92.7 ± 5.7% in 72 h). Differential Calorimetry and Fourier Transform Infrared Spectroscopy indicated that the drug and excipients were compatible and the drug was encapsulated into nanoparticles. The comparison of drug release profiles demonstrated that drug release from nanoparticles prepared with both higher molecular weight and higher concentration polymers decelerated but the drug release accelerated as the amount of glycolide in the copolymer composition increased. Weibull kinetic model was found to fit best for OND release from PLGA-PNPs. The cytotoxicity effect of the pure drug, marketed drug (Zofer®), and optimized formulations were tested in the L929 cell line, and the results exhibited that the cell viability of optimized pegylated formulation was higher than 90% after 48 h of incubation.

Design and Characterization of Agarose/HPMC Buccal Films Bearing Ondansetron HCl In Vitro and In Vivo: Enhancement Using Iontophoretic and Chemical Approaches.

The study was aimed at designing and characterizing the ondansetron hydrochloride (OND) bearing agarose (AG), and hydroxypropyl methyl cellulose (HPMC) mucoadhesive buccal films employing glycerol as a plasticizer. The buccal delivery of ondansetron hydrochloride was remarkably boosted by employing physical (iontophoresis) and chemical enhancement approaches (chemical penetration enhancers). To explore the influence of different formulation components, i.e., agarose, hydroxypropyl methyl cellulose (HPMC), and glycerol on various evaluating parameters, i.e., tensile strength, swelling index, ex vivo mucoadhesion time, and subsequently on in vitro drug release, a D-optimal design was opted. A buccal film bearing OND was mounted on bovine buccal mucosa for ex vivo permeation studies and impact of chemical and physical enhancement techniques on the permeation profile was also analysed. A linear release profile was revealed in in vitro drug release of OND over 60 minutes and outcomes ascertained the direct relationship between HPMC content and in vitro drug release and inverse relationship was depicted by AG content. The FTIR and DSC thermal analysis was executed to determine the physicochemical interactions and results exposed no chemical interactions between drug and polymers. The drug (OND) appeared as tiny crystals on smooth film surface during scanning electron microscopy (SEM) analysis. A notable enhancement in permeation flux, i.e., 761.02 μg/min of OND during ex vivo permeation studies was witnessed after the application of current (0.5-1 mA) without any time lag and with enhancement ratio of 3.107. A time lag of 15 minutes, 19 minutes, and 26 minutes with permeation flux of 475.34 μg/min, 399.35 μg/min, and 244.81 μg/min was observed after chemical enhancer pretreatment with propylene glycol, Tween 80, and passive, respectively. Rabbit was employed as the experimental animal for pharmacokinetic studies (in vivo) and cats for pharmacological activity (in vivo), and the results illustrated the enhanced bioavailablity (2.88 times) in the iontophoresis animal group when compared with the rabbits of control group. Likewise, a remarkable reduction in emesis events was recorded in cats of iontophoresis group. Conclusively, the histopathological examinations on excised buccal mucosa unveiled no severe necrotic or cytopathetic outcomes of current.

Unique green chromatography method for the determination of serotonin receptor antagonist (Ondansetron hydrochloride) related substances in a liquid formulation, robustness by quality by design-based design of experiments approach.

Serotonin receptor antagonist drug Ondansetron hydrochloride injectable formulation containing all related substances was identified and quantified by a single, simple, sensitive, eco-friendly, and green high-performance liquid chromatography method. The disseverment of all impurities was achieved with the Discovery Cyano (250 × 4.6) mm, 5μm column. The gradient program was composed of pH 5.7 phosphate buffer as mobile phase A and acetonitrile as mobile phase B. The flow rate, column compartment temperature, and detection wavelengths were 0.9 mL/min, 30°C, and 216 nm, respectively. The method was validated as per current regulatory guidelines. The obtained %relative standard deviation for the precision results was between 0.55 and 2.72% for all impurities. The correlation coefficient values from the linearity experiment for impurities and analyte were more than 0.995. The accuracy results were obtained between 88.4 and 113.0% for all impurities. Both sample and standard solutions showed 24 h stability at benchtop and refrigerator conditions. All impurities and analytes met the specificity and mass balance for all forced degradation conditions. Quality-by-design-based design of experiments was utilized to establish the method's robustness. Method greenness was assessed by using the current advanced tool green analytical procedure index, National Environmental Methods Index, and analytical eco-scale.

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

Fabrication And In-Vitro Analysis Of Mouth Dissolving Tablets Of Ondansetron Using Water Insoluble Super Disintegrant

In the present time, a mouth dissolving tablets become popular over conventional oral solid dosage form as it overcome common problem associated with conventional oral tablet dosage form such as issue in swallowing tablets in paediatric as well as geriatric population as well as avoid first pass metabolism and provide quick onset of action as it starts to absorb directly from oral cavity. Ondansetron HCl is used to prevent nausea and vomiting. In case of vomiting as well as in nausea, drug must require to act quickly to treat therapeutic condition of patient in need thereof. Therefore, combining Mouth dissolving technology with Ondansetron HCl as active pharmaceutical ingredient could be potential strategy to provide quick onset of action without swallowing entire tablet. Therefore, aim of the present research work is to fabricate mouth dissolving tablets of Ondansetron HCl using different concentration, i.e. 3%, 5% and 9%w/w, of different water insoluble super-disintegrants, namely Kollidon CL-SF, croscarmellose sodium and sodium starch glycolate. Batch F2 prepared using 6% Kollidon CL-SF with 2.5% sodium saccharine by direct compression method shown better taste masking as well as satisfied all mouth dissolving tablet criteria’s. Thus, it was concluded that taste masked mouth dissolving tablets of Ondansetron HCl could be successfully formulated by direct compression methods using 6% Kollidon CL-SF as water insoluble super-disintegrant that can effectively provide quick onset of action by eliminating need of administration of entire dosage form.

Effect of solvent fractions of crude extract of Liushenqu on gastrointestinal motility in guinea pigs, and the underlying mechanism(s)

Purpose: To study the effect of solvent fractions of the crude extract of liushenqu on gastrointestinal motility in guinea pigs, and the mechanism of action.
 Methods: The effects of solvent fractions of crude extract of liushenqu (LSQ) on receptors in guinea pig isolated small intestinal cells were determined by treatment with different receptor blockers, including diphenhydramine (0.067 mg/mL), atropine sulfate (0.064 mg/mL), propranolol hydrochloride (0.033mg/mL), phentolamine mesylate (0.04mg/mL) and ondansetron hydrochloride (0.048mg/mL), to investigate the possible pharmacological mechanism of action.
 Results: There was no significant change in the maximum amplitude of muscle tension before and after administration in the control group, petroleum ether fraction group, and dichlormethane fraction group, while muscle tension in the 95 % ethanol and n-butanol fractions significantly increased (p < 0.01). The mean changes in tension were significantly different from that of control group (p < 0.01), but ethyl acetate fraction showed significant intestinal muscle inhibition (p < 0.01). Addition of LSQ did not alleviate the inhibition caused by diphenhydramine, but it significantly reversed the inhibition caused by blockers of cholinergic muscarinic receptor, adrenergic alpha- and beta- receptors, and 5-HT receptor (p < 0.01).
 Conclusion: These results indicate that n-butanol fraction is the most effective bioactive fraction of LSQ, while ethyl acetate fraction has the opposite effect. In addition, its mechanism of action is related to increase in the amplitude of small intestine smooth muscle contraction and acceleration of small intestine peristalsis.

Fast-dissolving Sublingual Nanofibers of Ondansetron Hydrochloride: Formulation, Physicochemical Characterization, and Clinical Evaluation on Post-cataract Surgery Patients

Objective: Ondansetron hydrochloride (OND) is an antiemetic agent belongs to the 5-HT3 receptor antagonist class administrated widely in relieving nausea and vomiting which is the most common complication occurred after surgery. This study aimed to design and evaluate the physicochemical along with clinical effects of fast-dissolving nanofiber (FDN) of OND administrated sublingually to enhance the bioavailability, effectiveness, and patient compliance compared to orally disintegrating tablets (ODT). Methods: Nanofibers were prepared by the electrospinning method, using polyvinyl alcohol and alpha-cyclodextrin as polymers and sodium saccharin as the sweetener. Physicochemical and mechanical characteristics of nanofibers were examined then the clinical evaluation was performed. Eighty patients volunteering for cataract surgery were randomly divided into two groups, one received FDN, and the other treated with ODT of OND after recovery and in case of relieving nausea. The severity of nausea was assessed using a visual analogue scale in the 6 and 24 h intervals after drug administration. The SPSS 25.0 statistical software and statistical tests were used to analyze the obtained data. Results: Nanofibers possessed a mean diameter of 159 ± 30 nm beside suitable physicochemical and mechanical characteristics. Statistical evaluations showed that both FDN and ODT formulations had an equal anti-emetic effect (P>0.05) on reducing the severity of nausea but the FDN formulation caused significantly higher levels of patients’ satisfaction (P<0.05) compared to the ODT. Conclusions: Although both formulations had an almost equal anti-emetic effect, due to the benefits of this novel formulation including rapid disintegration, the ODT can be replaced by FDN.

Development, characterization, in vitro and ex vivo evaluation of antiemetic transdermal patches of ondansetron hydrochloride and dexamethasone

Development, characterization, in vitro and ex vivo evaluation of antiemetic transdermal patches of ondansetron hydrochloride and dexamethasone

Development, characterization, in vitro and ex vivo evaluation of antiemetic transdermal patches of ondansetron hydrochloride and dexamethasone

The idea of delivering drugs through skin is old, as the use is reported back in 16th century B.C. The husk of the castor oil plant in water was placed on an aching head. Today the transdermal drug delivery is well accepted for delivering drugs to the systemic circulation. The aim of this study was to design a compound transdermal patches containing ondansetrone HCL and dexamethasone for the treatment of nausea and vomiting in case of chemotherapy and regular symptom of nausea and vomiting. In the present work, an attempt has been made to develop a matrix-type transdermal therapeutic system comprising of Ondansetron-HCl and Dexamethasone in different ratios of hydrophilic and hydrophobic polymeric combinations with 15% w/v plasticizer and 5% w/v penetration enhancer were mixed with the polymer solution polymer were using solvent evaporation technique. The patches were further subjected to various characterization studies for prepared transdermal patches along with the thickness, tensile strength, folding endurance, % elongation, % moisture content, % moisture uptake, % drug content, In vitro drug permeation study on Franz diffusion cells. Obtained results showed no physical-chemical incompatibility between drugs and polymers. On the basis of results obtained from, tensile strength (18±0.16), folding endurance (126 ± 1 to 68 ± 2), % moisture content (2.9±0.4), % moisture uptake, % drug content (92.41 to 98.9 %), TPEC (Transdermal Patches of Ethyl Cellulose) was selected as optimized formulation. In vitro release of the selected batch, TPEC-1 followed by zero-order and formulation showed 62.69 % drug diffusion within 10 hours. Conclusively, the patches were considered to deliver drugs safely through the skin for a longer period often.

Does Intravenous Ondansetron Affect the Intestinal Motility Pattern in Healthy Donkeys (Equus asinus)?

The current study was undertaken to investigate the effect of intravenous administration of ondansetron on the small and large intestinal motility in donkeys (Equus asinus) using non-invasive transabdominal ultrasonography. The current prospective, randomized, placebo-controlled, crossover study was conducted on thirty healthy donkeys (15 males and 15 females). The selected donkeys underwent two trials; the first was performed by intravenous administration of saline solution as a placebo, while the second was carried out by intravenous administration of ondansetron hydrochloride. The contractility of selected portions of both the small intestine (duodenum and jejunum) and the large intestine (left colon, right colon, and cecum) was counted over a period of 3 minutes before administration (zero time) and at 15, 30, 60, 90, 120, 180, and 240 minutes after administration. The results of this study showed that ondansetron significantly altered the small and large intestinal contractility compared to normal saline. Intravenous administration of ondansetron induced a significant decrease in the duodenal, jejunal and cecal contractility compared to placebo at 30, 60, 90, and 120 minutes after administration. Likewise, ondansetron induced a significant decrease in the left colon and right colon contractility when compared with placebo at 30, 60, 90, 120, and 180 minutes following administration. Ondansetron can be used as a highly specific and selective serotonin 5-HT3 receptor antagonist for reducing the small and large intestinal motility in donkeys, and is therefore highly suggested for treating spasmodic colic in equine.

Development and Validation of RP-HPLC Method for Estimation of Ondansetron HCL in Bulk and Pharmaceutical Dosage Form

Development and Validation of RP-HPLC Method for Estimation of Ondansetron HCL in Bulk and Pharmaceutical Dosage Form

Novel potentiometric sensors for determination of ondansetron hydrochloride in pure and dosage form.

A new and sensitive potentiometric method has been developed and characterized for four novel sensors responsive to ondansetron hydrochloride. The potentiometric sensor method includes advancement of ondansetron hydrochloride sensors using a membrane comprised of molybdophosphoric acid (MPA) and ondansetron as an electro-active material in a polyvinylchloride (PVC) matrix membrane plasticized with di-butyl phthalate (DBPH), ortho-nitrophenyloctyl ether (O-NPOE), di-octyl phthalate (DOPH), or di-butyl phosphate (DBP). The validity of sensors in the present work has been examined, and steady and reproducible responses were obtained over the concentration ranges of 7.3 × 10−5 to 1.0 × 10−2, 6.6 × 10−6 to 1.0 × 10−2, 1.0 × 10−5 to 1.0 × 10−2, and 2.0 × 10−5 to 1.0 × 10−2 M for DBPH-, O-NPOE-, DOPH-, and DBP-ondansetron, respectively. The sensors revealed Nernstian gradients of 59.61 ± 0.50, 57.71 ± 0.23, 53.01 ± 0.14, and 53.20 ± 0.35 mV per decade individually with pH ranges of 2.5–5.5 in DBPH and 3.5–5.0 in O-NPOE electrodes, and 4.0–5.5 for both individual DOPH and DBP plasticized film-based sensors. The time responses for the sensors were 30, 32, 31, and 29 s for DBPH-, O-NPOE-, DOPH-, and DBP-ondansetron, respectively. The developed sensors also exhibited high selectivity towards ondansetron hydrochloride against different interfering species of inorganic particles with long-term stability of approximately 41, 36, 18, and multiple days for the DBPH, O-NPOE, DOPH, and DBP electrodes.

Formulation and Evaluation of Ondansetron HCl Nanoparticles for Transdermal Delivery

Ondansetron HCl (OND) is a potent antiemetic drug used for control of nausea and vomiting associated with cancer chemotherapy. It exhibits only 60 – 70 % of oral bioavailability due to first pass metabolism and has a relative short half-life of 3-5 hours. Poor bioavailability not only leads to the frequent dosing but also shows very poor patient adherence. Hence, in the present study an approach has been made to develop OND nanoparticles using eudragit® RS100 and eudragit® RL100 polymer to control release of OND for transdermal delivery and to improve patient compliance.
 Six formulas of OND nanoparticles were prepared using nanoprecipitation technique. The particles sizes and zeta potential were measured using zeta-plus analyzer. The particle morphology was also studied using scanning electron microscopy (SEM). The in-vitro release of the drug from the nanoparticles was carried out in phosphate buffer saline pH 7.4.
 The particle size of the prepared NPs were in nano size which ranged from (95.34 to 275.84 nm) with positive zeta potential. The drug entrapment efficiency was varied with the drug polymer ratio from 41.87% to 78.45%. The SEM showed uniform shape and regularly distributed particle sizes. The in-vitro drug release study exhibited the sustained release of OND with burst release. The cumulative percentage released after 12 hr. were between were 77.89 and 96.01%.
 Also the transdermal permeation study show that nanoparticles permeate more efficiently than aqueous solution of the drug through the skin by approximately two fold. OND nanoparticles were prepared successfully using nanoprecipitation method. The controlled drug release aimed for transdermal drug delivery could be obtained by using eudragit RS100 and eudragit RL100 polymers which can reduce dosing frequency, decrease side effects and improve patient compliance.

Development and Evaluation of IER based Formulation of Ondansetron HCl

Development and Evaluation of IER based Formulation of Ondansetron HCl

Determination of the stoichiometry between a drug and its counter-ion by supercritical fluid chromatography using ultra-violet and evaporative light scattering detections: Application to ondansetron hydrochloride

In this paper, a supercritical fluid chromatography method using ultra-violet and evaporative light scattering detections (SFC-UV/ELSD) has been developed and validated for the stoichiometry determination of an antiemetic drug with its counter-ion i.e. ondansetron hydrochloride. Seven stationary phases were first screened using a CO2-methanol-diethylamine mobile phase. Best conditions were determined using Derringer's desirability functions regarding chromatographic separation: selectivity, resolution, peak shape and runtime. The influence of co-solvent composition on resolution was evaluated. After optimization, best chromatographic results were obtained using 2-ethylpyridine stationary phase and a co-solvent composed of 0.2% diethylamine and 2% water in methanol. While ondansetron was quantified using UV detection (214 nm) and an external calibration curve, the determination of chloride was carried out using ELSD and an internal calibration curve. Then, the method was validated using the accuracy profile approach with a total error included in the ±10%. Finally, the proposed method was applied for the determination of the molar ratio between ondansetron and chloride. A value of 1.001 ± 0.003 demonstrated that the stoichiometry of this drug with its counter-ion was 1:1.

High frequency ultrasound mediated transdermal delivery of ondansetron hydrochloride employing bilosomal gel systems: ex-vivo and in-vivo characterization studies

Ondansetron hydrochloride (OND) suffers from rapid elimination (t1/2 = 3–4 h), moderate bioavailability (60%) and inconvenience following oral administration in emetic patients. As an alternative convenient approach, the current work explored the potential of high-frequency ultrasound (HFU) waves to promote transdermal delivery of OND via bilosomal gel systems (BGS) in an attempt to increase OND bioavailability and achieve a rapid onset of action in patients suffering from emesis. OND-loaded BGS were prepared and characterized for pH and rheologic properties. The variables influencing HFU were optimized, viz. bilosomal system: coupling-gel ratio (1:2 or 1:3), application period (5, 10 or 15 min) and (iii) ultrasound intensity (medium or high), mode (continuous or pulsed) & duty cycle (20, 50 or 100%). Ex-vivo permeation and confocal laser scanning microscopy (CLSM) studies were conducted. The best achieved BGS (BGS10-HFU) was subjected to histopathologic and pharmacokinetic studies in rats. OND-loaded BGS were shear thinning systems having tolerable pH values for skin application. The optimized HFU variables involved the utilization of a bilosomal system: coupling-gel ratio of 1:3 and the application of high intensity, continuous and 100% duty cycle ultrasound waves for 10 min. Ex-vivo permeation and CLSM studies revealed the superiority of BGS10 following HFU-pretreatment. BGS10-HFU exhibited minor histopathologic changes. Compared to an oral OND solution, BGS10-HFU system had significantly (P < 0.05) higher AUC0–24 and AUC 0–∞values. Non-significant differences between Cmax and tmax values were revealed. The best achieved system (BGS10-HFU) can increase OND bioavailability and initiate a rapid onset of action.

ESTIMATION OF ONDANSETRON HYDROCHLORIDE BY RP-HPLC

A RP-HPLC method was developed for the estimation of Ondansetron Hydrochloride in Bulk drug using high performance liquid chromatography. Ondansetron was a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic drug to treat nausea and vomiting after cancer chemotherapy. The separation was achieved by Promosil C-18 (250 mm x 4.6 mm x 10 µm) column because it allows higher separation and Acetonitrile: Methanol (50:50) as mobile phase with a flow rate of 1.2 ml/min. The detection was carried out at 216 nm. The retention time of drug was found 2.64 min. The developed method was validated. The proposed method shall prove equally effective to analyze Ondansetron Hydrochloride in the corresponding drug sample and may prove to be of great importance in pharmaceutical analysis. KEYWORDS: Ondansetron, Acetonitrile, Antiemetic, Methanol.

Formulation and evaluation of niosomal vesicles containing ondansetron HCL for trans-mucosal nasal drug delivery

Ondansetron HCl is a (5-HT3) serotonin receptor antagonist, used as anti-emetic drug in combination with anticancer agents. Conventional dosage forms have poor bioavailability and patient compliance. These problems can be reduced by the use of nasal niosomal thermo-reversible in situ gelling system. Niosomes were formulated using various surfactants (Span 60, Span 80, Tween 20, and Tween 80) in different ratios using the thin-film hydration technique. Niosomes were evaluated for particle size, zeta potential, transmission electron microscopy (TEM) imaging, drug entrapment efficiency, and in vitro drug release. Niosomes prepared using Span 60 and cholesterol in the ratio 1:1 (F5) showed higher entrapment efficiency (76.13 ± 1.2%) and in vitro drug release (91.76%) after 12 h was optimized. The optimized niosomes were developed into thermo-reversible in situ gel, composed of Poloxamer 407 and sodium carboxymethyl cellulose, prepared by cold method technique. Compatibility study (FTIR, DSC) was made for drugs and excipients that showed no significant interaction. The gel formulation G5 showed the most suitable gelation temperature (31 °C), viscosity (1250 mpoise), bioadhesion force (5860 ± 28 dyne/cm2), and in vitro drug release (70.6%) after 12 h. Comparative in vivo pharmacokinetic study on rabbits showed a sustained release and higher relative bioavailability of the prepared nasal in situ gel compared to similar dose of oral tablets (202.4%) which make ondansetron HCl niosomal nasal thermo-sensitive in situ gel a more convenient dosage form for the administration of ondansetron HCl than oral tablets.

Sustained release formulation of Ondansetron HCl using osmotic drug delivery approach

Ondansetron HCl (OSH) is a 5-HT3 receptor antagonist indicated for the prevention of nausea and vomiting associated with radiotherapy (adults: 8 mg, t.i.d) and/or chemotherapy (adults: 8 mg, b.i.d to t.i.d) and prevention of postoperative nausea and/or vomiting (adults: 8 mg, b.i.d). In elderly subjects, bioavailability may be somewhat higher (65%) and lower clearance, presumably due to reduced hepatic first-pass metabolism. OSH is extensively distributed in the body; about 70–75% of the drug in plasma is protein-bound and terminal elimination half-life is about 3 h after oral administration. The study was aimed to develop Push–pull Osmotic Pump (PPOP) bi-layered tablets for Ondansetron HCl ER tablets. The granulation was carried out using non-aqeous solvents followed by compression, seal coating, semi permeable coating, laser drilling (0.6 mm), and drug film coating with loading dose. The drug release was controlled by swelleable osmotic polymers of pull layer and push layer and orifice on the surface of tablet. The formulations were optimized for its core composition, extended release coating (Semipermeable membrane) polymer as to plasticizer ratio and orifice diameter. Optimized formulations were evaluated for micromeritic properties and in vitro drug release. The analytical methods were developed and validated to estimate in vitro drug potency, drug release, and in vivo pharmacokinetic parameters. Stability studies were done as per the ICH guidelines. The results of in vivo study concludes that the once OSH ER dose consistently maintains plasma concentration of drug within the therapeutic window over a period of 24 h.