Ondansetron/Cyclodextrin inclusion complex nanofibrous webs for potential orally fast-disintegrating antiemetic drug delivery.

Ondansetron (ODS) is an effective antiemetic drug which suffers from limited solubility and bioavailability during oral administration due to first-pass metabolism. However, these limitations can be mitigated through inclusion complexation with cyclodextrins (CDs). In this study, we have reported the electrospinning of polymer-free, free-standing ODS/CD nanofibrous webs (NW), a promising approach for developing a fast-disintegrating delivery system of an antiemetic drug molecule. Highly water soluble hydroxypropyl-beta-cyclodextrins (HPßCD) were used as both complexation agent and electrospinning matrix. The computational study revealed that the 1/2 (drug/CD) stoichiometry was more favorable compared to 1/1. The ODS/HPßCD NW was obtained with higher loading efficiency (∼96 %) compared to the control sample of ODS/polyvinyl alcohol (PVA) NW (∼80 %). The amorphous distribution of ODS raised by complexation and the highly water-soluble nature of HPßCD resulted into faster and better release profile and quite faster disintegration property (∼2 s) in artificial saliva than polymeric ODS/PVA NW. Here, ODS/HPßCD NW was generated in the absence of a toxic solvent or chemical to enable the drug loading in an amorphous state. From all reasons above, ODS/HPßCD NW might be a promising alternative to the polymeric based systems for the purpose of fast-disintegrating oral drug delivery.

Enantioseparation of ondansetron by countercurrent chromatography using sulfobutyl ether-ß-cyclodextrin as chiral selector.

Ondansetron, a highly selective 5-hydroxytryptamine 3 receptor antagonist, was successfully enantioseparated by recycling countercurrent chromatography using sulfobutyl ether-ß-cyclodextrin as chiral selector. Important factors for the enantioseparation were optimized, including different organic solvent, type of substituted ß-cyclodextrin, pH of aqueous phase, concentration of chiral selector, and separation temperature. A biphasic solvent system composed of n-hexane: n-butyl acetate: 0.1 mol/L phosphate buffer solution pH 9.2 with 50 mmol/L of sulfobutyl ether-ß-cyclodextrin (2.5:7.5:10, v/v/v) was selected. Under optimized separation conditions, 5 mg of ondansetron was enantioseparated using recycling countercurrent chromatography, yielding 1.2 and 1.5 mg of ondansetron enantiomers with 97.5 and 95.8% purity and the recovery reached 48-60%.

New and validated RP-HPLC Method for Quantification of Safinamide Mesylate in Presence of Its Basic Degradate, Levodopa and Ondansetron: Application to Human Plasma.

A simple, precise, rapid and accurate reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for analysis of safinamide mesylate (SAF) in presence of its basic degradate, and co-administered drugs levodopa and ondansetron. The mobile phase consisted of acetonitrile and 20 mM potassium dihyrogen orthophosphate buffer having pH = 5 (40: 60 v/v). Quantification was achieved with ultraviolet detector at 226 nm. The linear range was 0.5-10 µg/mL with mean recovery ± SD of 99.72 ± 1.59. The peak purity of SAF in pharmaceutical preparation spiked with its degradate and co-administered drugs revealed symmetry factor (999.8) within the calculated threshold (>998.1). The suggested method was validated in compliance with the International Conference on Harmonization (ICH) guidelines and statistically compared with the manufacturer HPLC method with no significant difference in terms of accuracy and precision. The assay method was successfully used to estimate SAF in tablets with good percentage recoveries. The high sensitivity (lower than Cmax of the drug 0.65 µg/mL) of the proposed HPLC method enabled the determination of SAF in presence of its basic degradate and co-administered drug, ondansetron in human plasma with acceptable accuracy. The suggested HPLC method could be used in Quality Control (QC) lab for analysis of the studied drug in pharmaceutical preparation.

Ondansetron buccal administration for paediatric use: A comparison between films and wafers.

The objective of this study was the development of different solid formulations, such as wafers and films, for buccal administration of ondansetron, a selective and potent antagonist of 5-hydroxytryptamine 3 receptors used in children for the treatment of nausea and vomiting. Wafers and films have been prepared drying an aqueous solution of pectin, hydroxypropyl methylcellulose, sodium hyaluronate, sodium carboxymethylcellulose, chitosan or gelatin, through lyophilization or oven. Formulations were characterized in terms of morphology, drug solid state and ability to hydrate, adhere to mucosa, release and favour the permeation of the drug through porcine esophageal epithelium, used as model of human buccal epithelium. The most promising formulations were tested for in vitro biocompatibility in human pulp fibroblasts. Films showed greater hydration and mucoadhesion abilities and allowed the release and the permeation of a greater amount of ondansetron with respect to wafers. Chitosan or hyaluronate provided films with the best mucoadhesion properties and good biocompatibility profile. Moreover, chitosan based film allowed to obtain the highest amount of permeated drug and could represent a novel child-appropriate dosage form able to combine the advantages of solid dosage form with the possibility to avoid the swallowing.

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.

Preparation of an oil suspension containing ondansetron hydrochloride as a sustained release parenteral formulation.

Ondansetron hydrochloride (ODS) is a selective 5-hydroxytryptamine type 3 antagonist for nausea and emesis prevention in neoplastic patients. To reduce dosing frequency and side effects and improve patient compliance, a sustained release parenteral formulation of ODS was developed. Microparticles of methylcellulose (MC) and ODS were prepared using the spray-drying method and suspended in oils to form oil suspensions. The formulations were evaluated for residual moisture, drug content, size distribution, DSC, XRD, FTIR, SEM, drug release, and pharmacokinetic studies. The effects of polymers and oils on the drug release were evaluated. MC showed the most prominent sustained release effect among various polymers examined with the optimum MC/ODS ratio of 2:1 (w/w). The particle size of the produced microparticles was in the mean diameter of approximately 3 µm. Physicochemical characterization suggested that ODS existed in an amorphous matrix within the microparticles and interacted with MC via hydrogen bonds. Corn oil was selected as the appropriate oil for suspension due to the sustained release of ODS and the appropriate viscosity. The optimized sustained release formulation of ODS was the corn oil suspension of spray-dried microparticles containing MC and ODS (2:1, w/w). It showed an in vitro drug sustained release up to 120 h, while the oil suspension of ODS without any polymer released the drug within 2 h. Following subcutaneous administration in rats, the optimized formulation could prolong the drug release until 72 h with the enhanced bioavailability in comparison with the ODS solution. The oil suspension of spray-dried microparticles might be an efficient approach for prolongation of the drug effect in the management of nausea and emesis. Graphical abstract.

Determination of some antiemetic drugs through its native fluorescence or fluorescence quenching of cerrous ammonium sulphate.

The manuscript describes two fluorimetric methods for the determination of some antiemetic drugs namely granisetron HCl, ondansetron HCl and tropisetron HCl, used in the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy. Granisetron HCl solution exhibits a native fluorescence, which can be applied for its determination at 365 nm upon excitation at 305 nm. The method was applied for the determination of granisetron HCl in drug substance, drug product as well as in presence of its acid induced degradation products. The quantum yield was calculated. The second proposed method is based on measuring the quenching effect induced by ondansetron HCl or tropisetron HCl on the fluorescence intensity of cerrous ammonium sulphate at λem 348 nm upon excitation at 250 nm in acidic medium. The analysis of quenching data showed that quenching of cerrous ammonium sulphate induced by ondansetron HCl or tropisetron HCl is mainly through dynamic quenching. Various variables affecting fluorescence response were studied and optimized. The obtained results were found to be statistically agreed with those obtained from the official or reported ones. Moreover, the validity of the methods was assessed according to ICH guidelines.

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Ondansetron.

Literature data pertaining to the physicochemical, pharmaceutical, and pharmacokinetic properties of ondansetron hydrochloride dihydrate are reviewed to arrive at a decision on whether a marketing authorization of an immediate release (IR) solid oral dosage form can be approved based on a Biopharmaceutics Classification System (BCS)-based biowaiver. Ondansetron, a 5HT3 receptor antagonist, is used at doses ranging from 4 mg to 24 mg in the management of nausea and vomiting associated with chemotherapy, radiotherapy, and postoperative treatment. It is a weak base and thus exhibits pH-dependent solubility. However, it is able to meet the criteria of "high solubility" as well as "high permeability" and can therefore be classified as a BCS class I drug. Furthermore, ondansetron hydrochloride 8 mg IR tablets (Zofran® 8 mg) and multiples thereof (16 mg = Zofran® 8 mg × 2 tablets and 24 mg = Zofran® 8 mg × 3 tablets) meet the criteria of "rapidly dissolving" in dissolution testing. Ondansetron hydrochloride has a wide therapeutic window and is well-tolerated after oral administration. Based on its favorable physicochemical properties, pharmacokinetic data and the minimal risks associated with an incorrect bioequivalence decision, the BCS-based biowaiver procedure can be recommended for ondansetron hydrochloride dihydrate IR tablets.

Rapid structure identification of nineteen metabolites of ondansetron in human urine using LC/MSn.

Ondansetron, a 5-hydroxytryptamine type 3 (5-HT3 ) receptor antagonist, is regarded as an excellent candidate to treat chemotherapy- and radiotherapy-induced nausea and vomiting. To better understand the metabolic profiles of ondansetron in human urine, the metabolites were analyzed using liquid chromatography/mass spectrometry (LC/MSn ). Urine samples were collected after oral administration of 8 mg ondansetron to healthy volunteers. Then samples were treated by solid-phase extraction and detected with LC/MSn . Besides ondansetron, in human urine, a total of 19 metabolites including 13 new metabolites were detected and identified via comparing the retention time and product ion spectra with those of reference standards isolated and characterized. The results showed that ondansetron was metabolized via hydroxylation, glucuronidation, sulfation and minor N-demethylation in human. LC/MSn was demonstrated to be useful and sensitive in the metabolic study of ondansetron.

Pharmacokinetics of R-(-)ondansetron compared with that of S-(-)ondansetron in rats using an LC-MS/MS method.

The pharmacokinetics of R-(-)ondansetron (R-ond) compared with that of S-(-)ondansetron (S-ond) was studied in rats. R-ond and S-ond were injected intravenously into rats at a dose of 2.0 mg/kg. The stability of ondansetron enantiomers in rat was determined by chiral HPLC, and the concentrations of R-ond and S-ond in plasma were determined by an LC/MS/MS method. The pharmacokinetic parameters were calculated and analyzed statistically using the t-test. The enantiomer inversions between R-ond and S-ond did not occur in rat. The pharmacokinetic parameters (t1/2 , AUC, MRT, CL) of R-ond and S-ond differed significantly. The concentration in plasma of the R/S-enantiomeric ratio reached a maximum value of 9.5 at 4.0 h post-dose. The pharmacokinetics of R-ond and S-ond are stereoselective in rat, which indicates substantial stereoselectivity in the disposition of ondansetron enantiomers in rat. R-ond has more potential than S-ond to be developed as a single enantiomer drug.

Identification of novel ondansetron metabolites using LC/MSn and NMR.

Ondansetron, a potent and highly sensitive 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, has been used for the treatment of chemotherapy- and radiotherapy-induced nausea and vomiting. The isolation and identification of ondansetron metabolites were investigated in our research. The feces and bile samples collected after oral administration of ondansetron were extracted and then isolated by semi-preparative HPLC. Then the pretreated samples were characterized by LC/MSn and NMR. In rats feces, a total of four metabolites were isolated and elucidated including 7-hydroxyl-ondansetron (M1), 8-hydroxyl-ondansetron (M2), 7-hydroxyl-N-desmethyl-ondansetron (M3), and 8-hydroxyl-N-desmethyl-ondansetron (M4). In addition, a kind of metabolite of phase II isolated in rats bile was characterized as N-desmethyl-ondansetron-7-O-ß-D-glucuronide (M5). To our knowledge, three metabolites were reported for the first time. LC/MSn and NMR-based approach was proved to be useful for full structure elucidation of unknown metabolites. The systematic metabolites isolation and elucidation provided metabolite reference standards for metabolites detection of ondansetron.

A novel unit-dose approach for the pharmaceutical compounding of an orodispersible film.

Orodispersible films (ODF) have clinical potential as extemporaneous pharmacy preparations for individualized pharmacotherapy. However, the conventional method of ODF preparation using a film applicator may limit its application, due to content uniformity challenges arising from viscosity changes of the casting solution and varied operator manipulation. This study proposes the unit-dose (UD) plate as an alternative to the film applicator for compounding individual ODFs. Using a design-of-experiments approach, we developed an extemporaneous ODF formulation for an antiemetic drug, ondansetron hydrochloride dihydrate (OND), at a clinically relevant dose. ODFs cast with the UD plate showed excellent content uniformity independent of the viscosity of the casting solution and drug concentration. Formulations were evaluated for performance with respect to patient acceptability and product quality. The effects of critical process parameters on critical quality attributes of the ODF were studied. HPMC concentration and volume of casting solution were the main factors affecting disintegration time and mechanical properties of the film, while drug concentration had no significant effect. However, further studies incorporating different drugs in larger concentration ranges are needed to investigate the impact of drug concentration and to establish a design space. Nevertheless, our results indicate the potential of using the UD plate to prepare ODFs with customized drug doses from a generic casting solution. Results from this study provide a framework for an extemporaneous ODF platform.

Enhanced transdermal delivery of ondansetron using nanovesicular systems: Fabrication, characterization, optimization and ex-vivo permeation study-Box-Cox transformation practical example.

This study aimed to formulate suitable nanovesicles (NVs) for transdermal delivery of Ondansetron. It also illustrated a practical example for the importance of Box-Cox transformation. A 23 full factorial design was used to enable testing transfersomes, ethosomes, and transethosomes of Ondansetron simultaneously. The independent variables (IVs) studied were sodium taurocholate amount, ethanol volume in hydration medium and sonication time. The studied dependent variables (DVs) were: particle size (PS), zeta potential (ZP) and entrapment efficiency (EE). Polynomial equations were used to study the influence of IVs on each DV. Numerical multiple response optimization was applied to select an optimized formula (OF) with the goals of minimizing PS and maximizing ZP absolute value and EE. Box-Cox transformation was adopted to enable modeling PS raised to the power of 1.2 with an excellent prediction R2 of 1.000. ZP and EE were adequately represented directly with prediction R2 of 0.9549 and 0.9892 respectively. Response surface plots helped in explaining the influence of IVs on each DV. Two-sided 95% prediction interval test and percent deviation of actual values from predicted ones proved the validity of the elucidated models. The OF was a transfersomal formula with desirability of 0.866 and showed promising results in ex-vivo permeation study.

Application of miniaturized near-infrared spectroscopy for quality control of extemporaneous orodispersible films.

Extemporaneous oral preparations are routinely compounded in the pharmacy due to a lack of suitable formulations for special populations. Such small-scale pharmacy preparations also present an avenue for individualized pharmacotherapy. Orodispersible films (ODF) have increasingly been evaluated as a suitable dosage form for extemporaneous oral preparations. Nevertheless, as with all other extemporaneous preparations, safety and quality remain a concern. Although the United States Pharmacopeia (USP) recommends analytical testing of compounded preparations for quality assurance, pharmaceutical assays are typically not routinely performed for such non-sterile pharmacy preparations, due to the complexity and high cost of conventional assay methods such as high performance liquid chromatography (HPLC). Spectroscopic methods including Raman, infrared and near-infrared spectroscopy have been successfully applied as quality control tools in the industry. The state-of-art benchtop spectrometers used in those studies have the advantage of superior resolution and performance, but are not suitable for use in a small-scale pharmacy setting. In this study, we investigated the application of a miniaturized near infrared (NIR) spectrometer as a quality control tool for identification and quantification of drug content in extemporaneous ODFs. Miniaturized near infrared (NIR) spectroscopy is suitable for small-scale pharmacy applications in view of its small size, portability, simple user interface, rapid measurement and real-time prediction results. Nevertheless, the challenge with miniaturized NIR spectroscopy is its lower resolution compared to state-of-art benchtop equipment. We have successfully developed NIR spectroscopy calibration models for identification of ODFs containing five different drugs, and quantification of drug content in ODFs containing 2-10mg ondansetron (OND). The qualitative model for drug identification produced 100% prediction accuracy. The quantitative model to predict OND drug content in ODFs was divided into two calibrations for improved accuracy: Calibration I and II covered the 2-4mg and 4-10mg ranges respectively. Validation was performed for method accuracy, linearity and precision. In conclusion, this study demonstrates the feasibility of miniaturized NIR spectroscopy as a quality control tool for small-scale, pharmacy preparations. Due to its non-destructive nature, every dosage unit can be tested thus affording positive impact on patient safety.

Stability of Alprazolam, Atropine Sulfate, Glutamine, Levofloxacin, Metoprolol Tartrate, Nitrofurantoin, Ondansetron Hydrochloride, Oxandrolone, Pregabaline, and Riboflavin in SyrSpend SF pH4 Oral Suspensions.

The objective of this study was to evaluate the stability of 10 commonly used active pharmaceutical ingredients compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend SF PH4): alprazolam 1.0 mg/mL, atropine sulfate 0.1 mg/mL, glutamine 250.0 mg/mL, levofloxacin 50.0 mg/mL, metoprolol tartrate 10.0 mg/mL, nitrofurantoin 2.0 mg/mL, ondansetron hydrochloride 0.8 mg/mL, oxandrolone 3.0 mg/mL, pregabaline 20.0 mg/mL, riboflavin 10.0 mg/mL. All suspensions were stored at both controlled refrigeration (2°C to 8°C) and controlled room temperature (20°C to 25°C). Stability was assessed by measuring the percent recovery at varying time points throughout a 90-day period. Active pharmaceutical ingredients quantification was performed by high-performance liquid chromatography via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredients + vehicle) was at least 90 days for all suspensions with regard to both temperatures. This suggests that the vehicle is stable for compounding active pharmaceutical ingredients from different pharmacological classes.

Evaluation of Pentravan®, Pentravan® Plus, Phytobase®, Lipovan® and Pluronic Lecithin Organogel for the transdermal administration of antiemetic drugs to treat chemotherapy-induced nausea and vomiting at the hospital.

The objective of this study was to evaluate five commercial ready-to-use transdermal vehicles (Phytobase®, Lipovan®, Pentravan®, Pentravan® Plus and Pluronic Lecithin Organogel (PLO)), for the compounding of three antiemetic drugs (ondansetron, dexamethasone and aprepitant) and their administration in combination to treat chemotherapy-induced nausea and vomiting (CINV) at the hospital. Drugs were individually formulated in these vehicles and in mixture in Pentravan® Plus using different penetration enhancers. Quality control of the forms has demonstrated that formulation process was mastered and convenient for the hospital (time required: 20min). Diffusion experiments through synthetic membranes and pig ear epidermis performed using Franz-type diffusion cells, have shown that the release and permeation process were greater for ondansetron than for dexamethasone and aprepitant, with a release step not limiting. As permeation of aprepitant was too low, it was discarded of the study. When ondansetron and dexamethasone were compounded in combination in Pentravan® Plus, the most efficient vehicle, a permeation decrease was observed. Finally, the use of tween 20 instead of EtOH as chemical enhancer has led to 2-fold factor increase in the flux of dexamethasone, resulting in fluxes convenient for transdermal administration of ondansetron to a child, but insufficient for an adult and for dexamethasone.

Nasal inserts containing ondansetron hydrochloride based on Chitosan-gellan gum polyelectrolyte complex: In vitro-in vivo studies.

The aim of this study was the production of ondansetron hydrochloride loaded lyophilized insert for nasal delivery. The nasal insert was prepared by the lyophilisation technique using Chitosan-gellan gum polyelectrolyte complex as the polymer matrix. The ondansetron loaded inserts were evaluated with respect to water uptake, bioadhesion, drug release kinetic study, ex vivo permeation study, and in vivo study. Lyophilised nasal inserts were characterized by differential scanning calorimetry, scanning electron microscopy and X-ray diffraction study. Scanning electron microscopy confirmed the porous sponge like structure of inserts whereas release kinetic model revealed that drug release followed non-fickian case II diffusion. The nasal delivery showed improved bioavailability as compared to oral delivery. In conclusion, the ondansetron containing nasal inserts based on Chitosan-gellan gum complex with potential muco-adhesive potential is suitable for nasal delivery.

Formulation and characterization of taste masked ondansetron-magnesium aluminum silicate adsorption systems.

CONTEXT: Taste masking greatly influences the acceptability of bitter tasting formulation; moreover, it governs the commercial and therapeutic success of drug products. OBJECTIVE: This work is directed toward masking the bitter taste of ondansetron HCl (ONS) utilizing the excipient, which can delay the reach of drug to the taste buds. MATERIAL AND METHODS: Magnesium aluminum silicate (Veegum F), a clay material having capability to adsorb the drugs onto it, was used. The adsorption systems of ONS with Veegum were obtained by dynamic adsorption technique and examined by scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) for morphology, thermal behavior, and interactions. The taste assessment of prepared systems was done by in vitro method based on drug release. RESULTS: The molecular interaction between ONS and Veegum in the system was revealed by FTIR spectroscopy. A change in thermal behavior of the system was observed owing to interaction or replacement of the cationic groups of Veegum with that of ONS. XRD studies revealed that the prepared system was having lower crystallinity as compared to ONS. The in vitro drug release study showed that ONS release from the system was relatively slow in basic environment than the acidic one. DISCUSSION: Adsorption of ONS on the surface of Veegum was mainly due to electrostatic interactions and hydrogen bonding. CONCLUSION: The experimental results reveal the successful intercalation of ONS into the space available between the layers of Veegum. Furthermore, this resulted in a control on drug release in salivary pH resulting in a concentration lower than bitterness threshold.

Synthesis of a novel superdisintegrant by starch derivatization with polysuccinimide and its application for the development of Ondansetron fast dissolving tablet.

CONTEXT: Disintegrants are the key excipients administered in tablet formulations to boost the decomposition of the tablet into smaller pieces in the gastrointestinal environment, thereby increasing the available surface area and enhancing a more rapid release of the active ingredient. OBJECTIVE: Polysuccinimide (PSI), a biodegradable polymer synthesized from aspartic acid, was reacted with starch and fully assessed by CHN, 1H-NMR, and FTIR. METHODS: PSI-grafted starch (PSI-St) was synthesized and applied as a disintegrant in the formulation of a rapidly disintegrating tablet of Ondansetron, a nausea and vomiting medicine. The tablet formulated with the newly developed superdisintegrant was evaluated for hardness, friability, disintegration time, and dissolution rate, and the results were compared with tablets formulated with an identical composition of test formulation differing only in type of disintegrant. RESULTS: Tablets prepared with starch and tablets prepared with sodium starch glycolate (SSG) were used as negative and positive controls, respectively. Dissolution study results indicated that although the onset of disintegration action was faster for SSG than PSI-St, higher amounts of drug were released from tablets formulated from PSI-St than from those formulated from SSG during 10 min. CONCLUSION: It was concluded that the novel synthesized superdisintegrant has an appropriate potential for the application in the formulation of fast dissolving tablets.

Synthesis of a novel superdisintegrant by starch derivatization with polysuccinimide and its application for the development of Ondansetron fast dissolving tablet.

CONTEXT: Disintegrants are the key excipients administered in tablet formulations to boost the decomposition of the tablet into smaller pieces in the gastrointestinal environment, thereby increasing the available surface area and enhancing a more rapid release of the active ingredient. OBJECTIVE: Polysuccinimide (PSI), a biodegradable polymer synthesized from aspartic acid, was reacted with starch and fully assessed by CHN, (1)H-NMR, and FTIR. METHODS: PSI-grafted starch (PSI-St) was synthesized and applied as a disintegrant in the formulation of a rapidly disintegrating tablet of Ondansetron, a nausea and vomiting medicine. The tablet formulated with the newly developed superdisintegrant was evaluated for hardness, friability, disintegration time, and dissolution rate, and the results were compared with tablets formulated with an identical composition of test formulation differing only in type of disintegrant. RESULTS: Tablets prepared with starch and tablets prepared with sodium starch glycolate (SSG) were used as negative and positive controls, respectively. Dissolution study results indicated that although the onset of disintegration action was faster for SSG than PSI-St, higher amounts of drug were released from tablets formulated from PSI-St than from those formulated from SSG during 10 min. CONCLUSION: It was concluded that the novel synthesized superdisintegrant has an appropriate potential for the application in the formulation of fast dissolving tablets.