An acryl resin-based swellable microneedles for controlled release intradermal delivery of granisetron.

Swellable microneedles (SMNs) are made of hydrogels and can deliver drug with controlled delivery rate by the cross-link density of the hydrogel. In this study, an acryl resin-based SMNs was developed for poorly water-soluble drugs. The making process of the SMNs is very simple and only need 60 min. The SMNs has high mechanical strength and is not easily broken. In-vitro release of SMNs-loaded model drug, granisetron base (GRB), was investigated. The results showed that seven days controlled release of GRB was obtained when SMNs contained pore-foaming agents (1.5% dicalcium phosphate (CaHPO4) and 1.5% polyvinylpyrrolidone (PVP)). The maximum amount delivered into skin was 86.158 ± 7.82% of the initial GRB (2.1 mg) loaded on SMNs preparation. Pharmacokinetics study in rats indicated a dose-dependent profile of plasma GRB concentrations and that the controlled release of 2.1 mg dose was observed for 144 hours. In conclusion, these SMNs provided a potential minimally invasive route for controlled-release systemic delivery of poorly water-soluble drugs.

Influence of the Component Excipients on the Quality and Functionality of a Transdermal Film Formulation.

The influence of formulation variables, i.e., a hydrophilic polymer (Methocel(®) E15) and a film-forming polymer (Eudragit(®) RL 100 and Eudragit(®) RS 100), on the physicochemical and functional properties of a transdermal film formulation was assessed. Several terpenes were initially evaluated for their drug permeation enhancement effects on the transdermal film formulations. D-Limonene was found to be the most efficient permeation enhancer among the tested terpenes. Transdermal film formulations containing granisetron (GRN) as a model drug, D-limonene as a permeation enhancer, and different ratios of a hydrophilic polymer (Methocel(®) E15) and a film-forming polymer (Eudragit(®) RL 100 or Eudragit(®) RS 100) were prepared. The prepared films were evaluated for their physicochemical properties such as weight variation, thickness, tensile strength, folding endurance, elongation (%), flatness, moisture content, moisture uptake, and the drug content uniformity. The films were also evaluated for the in vitro drug release and ex vivo drug permeation. The increasing ratios of Methocel(®):Eudragit(®) polymers in the formulation linearly and significantly increased the moisture content, moisture uptake, water vapor transmission rate (WVTR), and the transdermal flux of GRN from the film formulations. Increasing levels of Methocel(®) in the formulations also increased the rate and extent of the GRN release and the GRN permeation from the prepared films.

A high-performance liquid chromatography-tandem mass spectrometry method coupled with protein precipitation for determination of granisetron in human plasma and its application to a comparative pharmacokinetic study.

A rapid, simple and validated method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has been developed for the determination of granisetron in human plasma. Plasma samples were pre-purified by protein precipitation procedure. The chromatographic separation was achieved with Synergi Polar-RP (75 × 2 mm, 4 µm) column using a mixture of 5 mm pH4.0 ammonium formate and methanol (300:316, v/v) under isocratic conditions at a flow rate of 0.3 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. The analysis time was about 2.5 min. The method was fully validated over the concentration range 0.1-10 ng/mL. The lower limit of quantification was 0.1 ng/mL. Inter- and intra-batch precision was <6.1% and the accuracy was within 95.6-100.0%. The mean extraction recovery was 96.3%. Selectivity, matrix effect and stability were also validated. The method was applied to the comparative pharmacokinetic study of granisetron in Chinese healthy subjects.

Synthesis and characterization of photoaffinity probes that target the 5-HT3 receptor.

The 5-HT3 receptor is one of several ion channels responsible for the transmission of nerve impulses in the peripheral and central nervous systems. Until now, it has been difficult to characterize transmembrane receptors with classical structural biology approaches like X-ray crystallography. The use of photoaffinity probes is an alternative approach to identify regions in the protein where small molecules bind. To this end, we present two photoaffinity probes based on granisetron, a well known antagonist of the 5-HT3 receptor. These new probes show nanomolar binding affinity for the orthosteric binding site. In addition, we investigated their reactivity using irradiation experiments.

In vitro percutaneous absorption enhancement of granisetron by chemical penetration enhancers.

UNLABELLED: Granisetron (GRN), a potent antiemetic agent, is frequently used to prevent nausea and vomiting induced by cancer cytotoxic chemotherapy and radiation therapy. OBJECTIVE: As part of our efforts to further modify the physicochemical properties of this market drug, with the ultimate goal to formulate a better dosage form for GRN, this work was carried out to improve its permeability in vitro. METHODS: The permeation behavior of GRN in isopropyl myristate (IPM) was investigated across excised rabbit abdominal skin and the enhancing activities of three novel O-acylmenthol derivatives synthesized in our laboratory as well as five well-known chemical enhancers were evaluated. RESULTS: It was found that the steady-state flux of granisetron free base (GRN-B) was about 26-fold higher than that of granisetron hydrochloride (GRN-H). The novel enhancer, 2-isopropyl-5-methylcyclohexyl heptanoate (M-HEP), was observed to provide the most significant enhancement for the absorption of GRN-B. When incorporated in the donor solution with the optimal enhancer M-HEP, the steady-state flux of GRN-B increased from (196.44 ± 12.03) µg·cm⁻²·h⁻¹ to (1044.95 ± 71.99) µg·cm⁻²·h⁻¹ (P < 0.01). CONCLUSION: These findings indicated that the application of chemical enhancers was an effective approach to increase the percutaneous absorption of GRN in vitro.

Preparation and the in vitro evaluation of nanoemulsion system for the transdermal delivery of granisetron hydrochloride.

The objective of this study was to develop and evaluate nanoemulsion system for transdermal delivery of granisetron hydrochloride. Pseudo-ternary phase diagram was constructed to ascertain the concentration range of components of nanoemulsion composed of isopropyl myristate (IPM) as an oil phase, tween 85 as surfactant, ethanol as cosurfactant, water as aqueous phase. The effects of the content of IPM as an oil phase and n-methyl pyrrolidone (NMP) as transdermal enhancer on rat skin permeation of granisetron hydrochloride nanoemulsion were studied in vitro. The results showed that the mean particle size of nanoemulsion ranged from 50.4+/-1.5 to 82.4+/-0.9 nm with homogeneous size distribution. The resulted optimum formulation composed of 2.5% granisetron hydrochloride, 4% IPM, 40% tween 85/ethanol (1 : 1) and 10% NMP showed that the skin permeation rate was the highest (85.39+/-2.90 microg/cm(2)/h) and enhancement of drug permeability was 4.1-fold for transdermal delivery of granisetron hydrochloridein comparison with the control group (20% of tween 85 and 20% of ethanol micelle solution containing 2.5% of granisetron hydrochloride without IPM), and cumulative permeation amount was the highest (891.8+/-2.86 microg/cm(2)) with the shortest lag time (0.11+/-0.02 h) and was stable for at least 12 months. Therefore, the nanoemulsion system developed in this study offers a promising vehicle for the transdermal delivery system of granisetron hydrochloride, which may be as effective as oral or intravenous dosage forms and avoid some difficulties associated with these dosage forms.

Granisetron, an antiemetic drug, and its cobalt complex.

The crystal structures of granisetron [systematic name: 1-methyl-N-(9-methyl-9-azabicyclo[3.3.1]nonan-7-yl)indazole-3-carboxamide], C(18)H(24)N(4)O, (I), an antinauseant and antiemetic agent, and its Co(II) complex, diaqua[1-methyl-N-(9-methyl-9-azoniabicyclo[3.3.1]nonan-7-yl)indazole-3-carboxamide]cobalt(II) tetrachloride dodecahydrate, [Co(C(18)H(25)N(4)O)(2)(H(2)O)(2)]Cl(4).12H(2)O, (II), have been determined by X-ray diffraction. The granisetron molecule is in an extended conformation in both structures. Twisting of the central carboxamide group facilitates the Co(II) coordination in (II). The Co(II) atom is located on an inversion centre. The azabicyclononane ring adopts a chair-boat conformation in both structures. The molecules in (I) are linked into centrosymmetric dimers and form tetracyclic rings through C-H...O hydrogen-bonding interactions. The simultaneous presence of free chloride ions in conjunction with a number of hydration water molecules in (II) provides interesting hydrogen-bond patterns. This study can aid in the investigation of the properties of metal complexes with active pharmaceuticals in which the drug molecules play the role of a ligand.

Response surface methodology to optimize novel fast disintegrating tablets using ß cyclodextrin as diluent.

The objective of this work was to apply response surface approach to investigate main and interaction effects of formulation parameters in optimizing novel fast disintegrating tablet formulation using ß cyclodextrin as a diluent. The variables studied were diluent (ß cyclodextrin, X (1)), superdisintegrant (Croscarmellose sodium, X (2)), and direct compression aid (Spray dried lactose, X (3)). Tablets were prepared by direct compression method on B2 rotary tablet press using flat plain-face punches and characterized for weight variation, thickness, disintegration time (Y (1)), and hardness (Y (2)). Disintegration time was strongly affected by quadratic terms of ß cyclodextrin, croscarmellose sodium, and spray-dried lactose. The positive value of regression coefficient for ß cyclodextrin suggested that hardness increased with increased amount of ß cyclodextrin. In general, disintegration of tablets has been reported to slow down with increase in hardness. However in the present study, higher concentration of ß cyclodextrin was found to improve tablet hardness without increasing the disintegration time. Thus, ß cyclodextrin is proposed as a suitable diluent to achieve fast disintegrating tablets with sufficient hardness. Good correlation between the predicted values and experimental data of the optimized formulation validated prognostic ability of response surface methodology in optimizing fast disintegrating tablets using ß cyclodextrin as a diluent.

Development of Nasal Mucoadhesive Microspheres of Granisetron: A Potential Drug.

BACKGROUND: Granisetron is a serotonin 5-HT3 receptor antagonist used as an antiemetic to treat nausea and vomiting following chemotherapy and radiotherapy. Its main effect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata. OBJECTIVES: In this research mucoadhesive microspheres were developed in order to carry out the absorption of drug through nasal mucosa with the aim to improve therapeutic efficacy, avoid hepatic first pass metabolism and increase residence time. MATERIAL AND METHODS: Mucoadhesive microspheres of Granisetron using chitosan as polymer were prepared by emulsification cross-linking method to increase the residence time on the mucosa. The surface of prepared microspheres was characterized by SEM (Scanning electron microscopy) and evaluated for particle size, encapsulation efficiency, production yield, swelling ability, in-vitro mucoadhesion, in-vitro drug release and stability study. RESULT: Among all the formulations F6 with drug/polymer ratio of 1:3 displayed the best result. On drug release kinetic model study, all the formulations follow Zero order. Stability studies revealed that the microspheres kept at 25±2°C and 60±5% RH showed the maximum stability. CONCLUSION: After all the evaluation parameters and result obtained it can be said that these results confirmed the suitability of Granisetron mucoadhesive chitosan microspheres for nasal delivery system.

Effects of disintegration-promoting agent, lubricants and moisture treatment on optimized fast disintegrating tablets.

Effects of calcium silicate (disintegration-promoting agent) and various lubricants on an optimized beta-cyclodextrin-based fast-disintegrating tablet formulation were investigated. Effects of moisture treatment were also evaluated at 75, 85 and 95% relative humidities. A two factor, three levels (3(2)) full factorial design was used to optimize concentrations of calcium silicate and lubricant. Magnesium stearate, being commonly used lubricant, was used to optimize lubricant concentration in optimization study. Other lubricants were evaluated at an obtained optimum concentration. Desiccator with saturated salt solutions was used to analyze effects of moisture treatments. Results of multiple linear regression analysis revealed that concentration of calcium silicate had no effect; however concentration of lubricant was found to be important for tablet disintegration and hardness. An optimized value of 1.5% of magnesium stearate gave disintegration time of 23.4 s and hardness of 1.42 kg. At an optimized concentration, glycerol dibehenate and L-leucine significantly affected disintegration time, while talc and stearic acid had no significant effect. Tablet hardness was significantly affected with L-leucine, while other lubricants had no significant effect. Hardness was not affected at 75% moisture treatment. Moisture treatment at 85 and 95% increased hardness of the tablets; however at the same time it negatively affected the disintegration time.

Simultaneous Determination of Co-administrated Deflazacort, Aprepitant and Granisetron in Dosage Forms and Spiked Human Plasma by RP-HPLC/PAD.

A selective reversed phase high performance liquid chromatography/photodiode array detector (RP-HPLC/PAD) method has been developed for simultaneous determination of the three co-administrated deflazacort, aprepitant and granisetron drugs used with chemotherapy. The three cited drugs have been chromatographed on C18 column using a mobile phase consisting of acetonitrile-0.2% v/v triethylamine (80:20 v/v, pH of 6.6 ± 0.05) with isocratic elution and monitored by photodiode array at 220 nm. International conference on harmonization (ICH) guidelines were followed to validate the developed method. Successful application of the developed method was assessed by the simultaneous determination of the studied drugs in pure forms, dosage forms and plasma samples in the ranges of 0.2-20, 0.4-40 and 0.2-20 µg/mL for deflazacort, aprepitant and granisetron, respectively.

Mapping the Orthosteric Binding Site of the Human 5-HT3 Receptor Using Photo-cross-linking Antagonists.

The serotonin-gated 5-HT3 receptor is a ligand-gated ion channel. Its location at the synapse in the central and peripheral nervous system has rendered it a prime pharmacological target, for example, for antiemetic drugs that bind with high affinity to the neurotransmitter binding site and prevent the opening of the channel. Advances in structural biology techniques have led to a surge of disclosed three-dimensional receptor structures; however, solving ligand-bound high-resolution 5-HT3 receptor structures has not been achieved to date. Ligand binding poses in the orthosteric binding site have been largely predicted from mutagenesis and docking studies. We report the synthesis of a series of photo-cross-linking compounds whose structures are based on the clinically used antiemetic drug granisetron (Kytril). These displaced [3H]granisetron from the orthosteric binding site with low nanomolar affinities and showed specific photo-cross-linking with the human 5-HT3 receptor. Detailed analysis by protein-MS/MS identified a residue (Met-228) near the tip of binding loop C as the covalent modification site.

Cutaneous adverse drug reactions during chemotherapy: consider non-antineoplastic drugs.

Cutaneous adverse drug reactions (CADR) during chemotherapy are not rare, but difficult to manage. Case 1, a 49-year-old man was treated with 5-fluorouracil, irinotecan, and oxaliplatin for a pancreatic tumour. He developed a generalized urticaria during his seventh course of chemotherapy. 2 months later, skin tests determined a granisetron allergy with an ondansetron cross-reaction. Substituting the anti-emetic allowed continuation of the chemotherapy. Case 2, a 44-year-old woman, having recurring breast cancer that was treated with doxorubicin, and docetaxel developed a maculo-papular rash (MPR) the day after the first chemotherapy treatment. 2 weeks later, skin tests determined a corticosteroid class A allergy. Using a class C corticosteroid, no other reaction occurred. Case 3, a 44-year-old woman, having breast cancer treated with 5-fluorouracil, cyclophosphamide, and epirubicin developed an MPR after the second chemotherapy treatment. 12 days later, skin tests showed a granisetron allergy. Using alizapride, chemotherapy was continued with no further reaction. CADR necessitate a thorough investigation, modified according to the patient's chemotherapy treatment chronology and precautions while testing the molecules. Tests are rarely carried out, however, these tests allow for continuation of effective chemotherapy once the responsible agent has been determined. The 3 cases reported underline the role of complementary treatment and the necessity to test those molecules.

Thermal and non-thermal methods to evaluate compatibility of granisetron hydrochloride with tablet excipients.

Compatibility of granisetron hydrochloride with selected excipients was assessed using Differential Scanning Calorimetry (DSC) as a thermal screening technique. Non-thermal methods like Fourier Transform Infrared spectroscopy and Thin Layer Chromatography were used as complementary techniques to adequately support and assist in interpretation of DSC results. Some drug-excipient interaction was observed with beta-cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin, mannitol, and magnesium stearate in DSC studies. However, further evaluation of these incompatible excipients with non-thermal methods showed that these excipients were compatible with granisetron hydrochloride. Non-thermal methods were, thus, of help in interpreting DSC results and excluding all relevant pharmaceutical incompatibilities.

Compatibility and Stability of VARUBI (Rolapitant) Injectable Emulsion Admixed with Intravenous Granisetron Hydrochloride.

Prophylaxis or therapy with a combination of a neurokinin 1 (NK-1) receptor antagonist (RA), a 5-hydroxytryptamine- 3 (5-HT3) RA, and dexamethasone is recommended by international antiemesis guidelines for the prevention of chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy and for select patients receiving moderately emetogenic chemotherapy. VARUBI (rolapitant) is a substance P/NK-1 RA that was recently approved by the U.S. Food and Drug Administration as an injectable emulsion in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. Granisetron Hydrochloride Injection USP is one of the 5-HT3 RAs indicated for the prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin. Herein, we describe the physical and chemical compatibility and stability of VARUBI (rolapitant) injectable emulsion (166.5 mg/92.5 mL [1.8 mg/mL], equivalent to 185 mg of rolapitant hydrochloride) admixed with Granisetron Hydrochloride Injection USP (1.0 mg/mL, equivalent to 1.12 mg/mL hydrochloride). Binary admixtures of VARUBI injectable emulsion and Granisetron Hydrochloride Injection USP were prepared and stored in VARUBI ready-to-use glass vials and in four types of commonly used intravenous administration (tubing) sets. Evaluation of the physical and chemical compatibility and stability of the admixtures in the VARUBI ready-to-use vials stored at room temperature (20°C to 25°C) under fluorescent light and under refrigeration (2°C to 8°C protected from light) was conducted at 0, 1, 6, 24, and 48 hours, and that of the admixtures in the intravenous tubing sets was evaluated at 0, 2, and 6 hours of storage at 20°C to 25°C. Physical stability was evaluated by visual examination of the container contents under normal room light, and measurement of turbidity, globule size, and particulate matter. Chemical stability was assessed by measuring the pH of the admixture and determining drug concentrations (potency) and impurity levels by high-performance liquid chromatographic analysis. The pH, turbidity, globule size, and particulate matter of all samples remained within narrow and acceptable ranges at all study time points, indicating that combining the two formulations into a binary admixture is physically and chemically compatible and stable. VARUBI injectable emulsion admixed with Granisetron Hydrochloride Injection USP demonstrated compatibility and stability in a ready-to-use glass vial for at least 24 hours at room temperature and 48 hours under refrigeration, as well as in the four intravenous tubing sets for at least 6 hours at 20°C to 25°C. No decrease of drug concentration (or potency) of any admixed components occurred in the samples stored at the two conditions and time periods studied based on high-performance liquid chromatographic analysis. The levels of impurities stayed below the safety limits set by International Conference on Harmonisation during the study period.

Development of novel bioadhesive granisetron hydrochloride spanlastic gel and insert for brain targeting and study their effects on rats.

The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive gels and lyophilized inserts for intranasal administration to improve GH bioavailability and brain targeting. Carpapol 934 and HPMC were incorporated in GH spanlastic in nasal gels (GHSpNGs). Gelatin and HPMC as matrix former, glycine as a collapse protecting and mannitol as an insert filler and sweeting agent were used to prepare GH spanlastic loaded in lyophilized inserts (GHSpNIs). The prepared GHSpNGs were characterized for pH measurement, drug content, rheology, and in vitro drug release. The prepared GHSpNIs were characterized for drug content, surface pH, GH release, and mucoadhesion. Biological investigations including pharmacokinetics studies and brain drug targeting efficiency dimensions were performed on rats (LC-MS/MS). The results showed thixotropic pseudoplastic gels and white insert with pH values in a physiological range, drug content (89.9-98.6%), (82.4-98.38%) for gel and insert, respectively and rapid release rate of GH. Biological studies showed that Cmax and AUC0-6 h in brain and plasma after intranasal administration of gel and insert were higher compared to IV administration of GH solution. A high brain targeting efficiency (199.3%, 230%) for gel and insert, respectively and a direct nose to brain transport (49.8%, 56.95%) for gel and insert, respectively confirmed that there is a direct nose to brain transport of GH following nasal administration of GH spanlastic loaded in nasal gel and insert. GHSpNIs can be considered as potential novel drug delivery system intended for brain targeting via the nasal rout of administration than GHSpNGs.

Design, Optimization and Characterization of Granisetron HCl Loaded Nano-gel for Transdermal Delivery.

BACKGROUND & OBJECTIVE: Our research objective was to design, develop, optimize and characterize Granisetron HCl transdermal gel in order to minimize side effects associated with oral delivery. METHOD: A statistical design was practically applied for further optimization and preparation of transfersomal gel using Box-Behnken methodology at three levels. The selected independent and dependent variables were Lipoid, surfactant and sonication time and encapsulation efficiency, size and flux correspondingly. RESULT: The optimized formulation (GTV-16) morphology, shape, size, potential, encapsulation capacity and flux (using Franz-diffusion cell assembly via animal skin barricade medium) were determined. Then, GTV-16 incorporated into gel and during evaluation nano-transformal gel has good particle size of 127.7±1.08 nm, better entrapment efficiency of 83.0 ± 3.22 % and flux of 20.0 ± 1.88µgcm-2/h. CONCLUSION: The results demonstrated that Granisetron Hydrochloride loaded nano-gel was significantly superior with 8.5 fold enhancement in bioavailability as compared with drug solution.

The binding orientations of structurally-related ligands can differ; A cautionary note.

Crystal structures can identify ligand-receptor interactions and assist the development of novel therapeutics, but experimental challenges sometimes necessitate the use of homologous proteins. Tropisetron is an orthosteric ligand at both 5-HT3 and α7 nACh receptors and its binding orientation has been determined in the structural homologue AChBP (pdbid: 2WNC). Co-crystallisation with a structurally-related ligand, granisetron, reveals an almost identical orientation (pdbid; 2YME). However, there is a >1000-fold difference in the affinity of tropisetron at 5-HT3 versus α7 nACh receptors, and α7 nACh receptors do not bind granisetron. These striking pharmacological differences prompt questions about which receptor the crystal structures most closely represent and whether the ligand orientations are correct. Here we probe the binding orientation of tropisetron and granisetron at 5-HT3 receptors by in silico modelling and docking, radioligand binding on cysteine-substituted 5-HT3 receptor mutants transiently expressed in HEK 293 cells, and synthetic modification of the ligands. For 15 of the 23 cysteine substitutions, the effects on tropisetron and granisetron were different. Structure-activity relationships on synthesised derivatives of both ligands were also consistent with different orientations, revealing that contrary to the crystallographic evidence from AChBP, the two ligands adopt different orientations in the 5-HT3 receptor binding site. Our results show that even quite structurally similar molecules can adopt different orientations in the same binding site, and that caution may be needed when using homologous proteins to predict ligand binding.

Hydrophilic interaction liquid chromatography in analysis of granisetron HCl and its related substances. Retention mechanisms and method development.

In this paper separation of granisetron and its two related substances in HILIC mode is presented. Separation was done on silica column derivatized with sulfoalkylbetaine groups (ZIC-HILIC). Firstly, retention mechanisms were assessed whereby retention factors of substances were followed in wide range of acetonitrile content (80-97%), at constant concentration of aqueous buffer (10mM) as well as at constant pH value of 3.0. Further, in order to developed optimal HILIC method, Design of Experiments (DoE) methodology was applied. For optimization full factorial design 3(2) was employed. Influence of acetonitrile content and ammonium acetate concentration were investigated while pH of the water phase was kept at 3.3. Adequacy of obtained mathematical models was confirmed by ANOVA. Optimization goals (α>1.15 and minimal run time) were accomplished with 94.7% of acetonitrile in mobile phase and 70 mM of ammonium acetate in water phase. Optimal point was in the middle of defined Design Space. In the next phase, robustness was experimetally tested by Rechtschaffen design. The investigated factors and their levels were: acetonitrile content (±1%), ammonium acetate molarity in water phase (±2 mM), pH value of water phase (±0.2) and column temperature (±4 °C). The validation scope included selectivity, linearity, accuracy and precision as well as determination of limit of detection (LOD) and limit of quantification (LOQ) for the related substances. Additionally, the validation acceptance criteria were met in all cases. Finally, the proposed method could be successfully utilized for estimation of granisetron HCl and its related substances in tablets and parenteral dosage forms, as well as for monitoring degradation under various stress conditions.

Development and evaluation of a sublingual film of the antiemetic granisetron hydrochloride.

The objective of this study was to develop an oral transmucosal formulation of an antiemetic drug that can not only serve in the active form but also provide a controlled release profile. In this study, sublingual films based on the biodegradable and water-soluble polymers, that is HPMCK-4M and PVPK-30, were developed by the solvent casting method, and were loaded with the antiemetic drug granisetron hydrochloride (granisetron HCl). The entrapment efficiency of the developed formulation was found to be 86%. The in vitro profile showed an instant release of the drug from the sublingual film, in a pattern following the first order kinetics array. The in vivo studies showed that granisetron HCl was delivered in its active state and showed effective results, as compared to its activity in the marketed formulation.