Formulation studies for mirtazapine orally disintegrating tablets

Abstract

Objective: Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab).

Materials and methods: Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900?mL 0.1?N HCl medium, 900?mL pH 6.8 phosphate buffer or 900?mL pH 4.5 acetate buffer at 37?±?0.2?°C as dissolution medium.

Results: Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media.

Discussion: Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles.

Conclusion: Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.     

Preparation and evaluation of orally disintegrating tablets of taste masked phencynonate HCl using ion-exchange resin

This study was intended to design an orally disintegrating tablet (ODT) formulation that can mask the extremely bitter and metallic taste of phencynonate HCl by novel ion-exchange resins. The drug–resin complexes (DRCs) were prepared and characterized by scanning electron microscopy, X-ray powder diffraction and differential scanning calorimetry. In vitro properties (dissolution, wetting time and disintegration time) and in vivo behavior (disintegration time and taste-masking effect) in healthy volunteers of the prepared ODTs were also investigated. The drug was changed from the crystal structure to the amorphous form in the DRC. Compared with commercial tablets, the in vitro and in vivo disintegration of optimized DRC-loaded ODTs with a drug-resin ratio of 1:1 was greatly improved and better palatability with a low bitterness index (0.33) was obtained. The current DRC-loaded ODT could promise a good way to mask the unpleasant taste of certain drugs and accordingly improve the patient compliance.     

Formulation and evaluation of meloxicam oral disintegrating tablet with dissolution enhanced by combination of cyclodextrin and ion exchange resins

Context: The bitter taste of drug is masked by the exchange of ionized drugs with counter ions of ion exchange resin, forming “resinate”. Cyclodextrin reduces the unpleasant taste and enhances the drug solubility by encapsulating drug molecules into its central cavity.

Objective: Oral disintegrating tablets (ODTs) using the combination of ion exchange resin and cyclodextrin was developed, to mask the bitter taste and enhance drug dissolution.

Methods: Meloxicam (MX) was selected as a model drug. Formulations containing various forms of MX (free drug, MX-loaded resin or resinate, complexes of MX and 2-hydroxypropyl-β-cyclodextrin (HPβCD) or MX/HPβCD complexes, and a mixture of resinate and MX/HPβCD complexes) were made by direct compression. The ODTs were evaluated for weight variation, thickness, diameter, hardness, friability, disintegration time, wetting time, MX content, MX release, degree of bitter taste and stability.

Results and discussion: The tablet hardness was ～3?kg/in², and the friability was <1%. Tablets formulated with resinate and the mixture of resinate and MX/HPβCD complexes disintegrated rapidly within 60?s, which is the acceptable limit for ODTs. These results were corresponded to the in vivo disintegration and wetting times. However, only tablets containing the mixture of resinate and MX/HPβCD complexes provided complete MX dissolution and successfully masked the bitter taste. In addition, this tablet was stable at least 6 months.

Conclusions: The combination of ion exchange resin and cyclodextrin could be used in ODTs to mask the bitter taste and enhance the dissolution of drugs that are weakly soluble in water.     

Chlorogenic acid stabilized nanostructured lipid carriers (NLC) of atorvastatin: formulation,design and in vivo evaluation

The present work was aimed at developing an optimized oral nanostructured lipid carrier (NLC) formulation of poorly soluble atorvastatin Ca (AT Ca) and assessing its in vitro release, oral bioavailability and pharmacodynamic activity. In this study, chlorogenic acid, a novel excipient having synergistic cholesterol lowering activity was utilized and explored in NLC formulation development. The drug-loaded NLC formulations were prepared using a high pressure homogenization technique and optimized by the Box-Behnken statistical design using the Design-Expert software. The optimized NLC formulation was composed of oleic acid and stearic acid as lipid phase (0.9% w/v), poloxamer 188 as surfactant (1% w/v) and chlorogenic acid (0.05% w/v). The mean particle size, polydispersity index (PDI) and % drug entrapment efficiency of optimized NLC were 203.56?±?8.57?nm, 0.27?±?0.028 and 83.66?±?5.69, respectively. In vitro release studies showed that the release of drug from optimized NLC formulations were markedly enhanced as compared to solid lipid nanoparticles (SLN) and drug suspension. The plasma concentration time profile of AT Ca in rats showed 3.08- and 4.89-fold increase in relative bioavailability of developed NLC with respect to marketed preparation (ATORVA® tablet) and drug suspension, respectively. Pharmacodynamic study suggested highly significant (**p?0.01) reduction in the cholesterol and triglyceride values by NLC in comparison with ATORVA® tablet. Therefore, the results of in vivo studies demonstrated promising prospects for successful oral delivery of AT Ca by means of its chlorogenic acid integrated NLC.     

Dual-purpose vardenafil hydrochloride/dapoxetine hydrochloride orodispersible tablets: in vitro formulation/evaluation,stability study and in vivo comparative pharmacokinetic study in healthy human subjects

Erectile dysfunction (ED) is the most important disorder after premature ejaculation for sexual activity in men. Vardenafil hydrochloride (VH) is an oral therapy for the treatment of erectile dysfunction. VH oral disintegrating tablets (ODTs) have been prepared by freeze drying technique to improve its dissolution profile and the overall clinical performance. Dapoxetine hydrochloride (DH) was added to the best three formulae of the prepared VH ODTs to treat premature ejaculation. All the ODTs formulae were evaluated for weight variation, friability, drug content, in vitro disintegration time, wetting time, and the dissolution study. Gelatin as a matrix former with N-methylpyrrolidone as a solubilizer in VH/DH ODTs improved the dissolution rate and extent of release of VH and DH with 100% of drug being dissolved after 15?min. In vivo study results from six healthy male volunteers showed shorter T_max of VH from VH/DH ODT of 0.583?±?0.129?h and shorter T_max of DH from VH/DH ODT of 0.625?±?0.137?h and showed AUC_0–12 of VH from VH/DH ODT of 39.234?±?10.932?ng/ml^?h¹ and AUC_0–12 of DH from VH/DH ODT of 531.681?±?129.544?ng/ml^?h¹, with relative bioavailability values of 100.9 and 85%, respectively, compared to (Levitra^®) and (Priligy^®).     

Novel taste-masked orally disintegrating tablets for a highly soluble drug with an extremely bitter taste: design rationale and evaluation

The purpose of this study was to evaluate the taste masking potential of novel solid dispersions (SDs) using Eudragit^® EPO as the excipient when incorporated into the orally disintegrating tablets (ODTs) for delivering a highly soluble drug with an extremely bitter taste. The pyridostigmine bromides (PB) SDs (PBSDs) were prepared by solvent evaporation–deposition method. The physicochemical properties of PBSDs were investigated by means of differential scanning calorimetry and Fourier transformed infrared spectroscopy. The dissolution test showed that only about 8% of PB was released from PBSDs in the simulated salivary fluid in 30 s. Therefore, PBSDs were considered taste-masked and selected for formulation of PBODTs. A central composite design was employed for process optimization. Multiple linear regression analysis for process optimization revealed that the optimal PBODTs were obtained, when the microcrystalline cellulose and crospovidone were 17.16 and 5.55 (%, w/w), respectively, and the average in vivo disintegration time was 25 s. The bitterness threshold of PB was examined by a sensory test, and the threshold value was set as 3?mg in each tablet. Taste evaluation of PBODTs in 18 volunteers revealed considerable taste masking with bitterness below the threshold value. PBODTs also revealed rapid drug release (around 99%, 2?min) in the simulated gastric fluid. The mean PB plasma concentration–time profiles of PBODTs and that of the commercial tablets were comparable, with closely similar pattern. Bioequivalence assessment results demonstrated that PBODTs and the commercial tablets were bioequivalent. In conclusion, PBODTs are prepared successfully, with taste masking and rapid disintegration in the oral cavity.     

In vitro and in vivo investigation of taste-masking effectiveness of Eudragit E PO as drug particle coating agent in orally disintegrating tablets

Abstract

Context: Considering that bitter taste of drugs incorporated in orally disintegrating tablets (ODTs) can be the main reason for avoiding drug therapy, it is of the utmost importance to achieve successful taste-masking. The evaluation of taste-masking effectiveness is still a major challenge.

Objective: The objective of this study was to mask bitter taste of the selected model drugs by drug particle coating with Eudragit^® E PO, as well as to evaluate taste-masking effectiveness of prepared ODTs using compendial dissolution testing, dissolution in the small-volume shake-flask assembly and trained human taste panel.

Materials and methods: Model drugs were coated in fluidized bed. Disintequik? ODT was used as a novel co-processed excipient for ODT preparation. Selected formulations were investigated in vitro and in vivo using techniques for taste-masking assessment.

Results and discussion: Significantly slower drug dissolution was observed from tablets with coated drug particles during the first 3?min of investigation. Results of in vivo taste-masking assessment demonstrated significant improvement in drug bitterness suppression in formulations with coated drug. Strong correlation between the results of drug dissolution in the small-volume shake-flask assembly and in vivo evaluation data was established (R?≥?0.970).

Conclusion: Drug particle coating with Eudragit^® E PO can be a suitable approach for bitter taste-masking. Strong correlation between in vivo and in vitro results implicate that small-volume dissolution method may be used as surrogate for human panel taste-masking assessment, in the case of physical taste-masking approach application.     

Design,development and in-vitro evaluation of diclofenac taste-masked orodispersible tablet formulations

Context: Fast onset of action is prerequisite for acute pain medication. A palatable orodispersible medicine of diclofenac providing rapid analgesic effect should improve patient compliance and treatment.

Objective: In the present study, diclofenac taste-masked orodispersible tablets (ODTs) with fast release characteristics were developed. Different taste-masking approaches and formulation concepts were screened in vitro for candidate selection.

Materials and methods: Diclofenac was used as free acid. Five taste-masked microgranule formulations were prepared by wet granulation and/or coating processes, and compressed to ODTs. Citric acid (pH-modifying agent) and Eudragit® E PO (amino methacrylate copolymer) were used as taste-masking agents. Evaluation criteria were (i) disintegration time, (ii) processability and (iii) in-vitro dissolution profiles in simulated saliva (pH 7.4, 5?mL, 3?min) and compendial pH-change media (paddle, 50?rpm). The prototypes were compared to reference ODTs (without taste-masking). Most suitable ODT prototypes were selected and further evaluated for taste-masking efficiency using an electronic tongue.

Results and discussion: In simulated saliva, the drug was slower released from the prototypes (between 1.1% and 15.5%) than from reference ODTs (23.7%). Less dissolved particles are thus expected in vivo for taste perception. Two ODT prototypes showed fast and complete drug release in phosphate buffer. The formulation providing the most efficient taste-masking was selected guided by electronic tongue data.

Conclusion: A novel palatable and fast acting diclofenac ODT formulation was successfully developed. Formulation design, development and in-vitro evaluation used in this study may serve as rational approach for manufacturing taste-masked orodispersible dosage forms.     

Fabrication and in vitro evaluation of bidirectional release and stability studies of mucoadhesive donut-shaped captopril tablets

Objective: To obtain controlled release of captopril in the stomach, coated, mucoadhesive donut-shaped tablets were designed.

Materials and methods: Donut-shaped tablet were made of different ratios of diluents to polymer or combination of polymers by direct compression method. Top and bottom portions of the tablet were coated with water-insoluble polymer followed by mucoadhesive coating. Time of water penetration, measurement of tensile strength, mucoadhesion studies (static ex vivo and ex vivo wash-off) were taken into account for characterization of respective films. In vitro study has been performed at different dissolution mediums. Optimized batches were also prepared by wet granulation. Stability studies of optimized batches have been performed.

Results: The results of time of water penetration and tensile strength indicated positive response against water impermeation. Mucoadhesive studies showed that film thickness of 0.12?mm was good for retention of tablet at stomach. At pH 1.2, optimized batch of tablet made with hydroxypropyl methyl cellulose (HPMC) E15 as binder showed 80% w/w drug release within 4–5?h with maximum average release of 97.49% w/w. Similarly, maximum average releases of 96.36% w/w and 95.47% w/w were obtained with nearly same dissolution patterns using combination of HPMC E5 and HPMC E50 and sodium salt of carboxy methyl cellulose (NaCMC) 500–600 cPs instead of HPMC E15. The release profiles in the distilled water and pH 4.5 followed the above pattern except deviation at pH 6.8. Stability studies were not positive for all combinations.

Conclusion: Coated, mucoadhesive donut-shaped tablet is good for controlled release of drug in the stomach.     

Development and optimization of taste-masked orally disintegrating tablets (ODTs) of clindamycin hydrochloride

The purpose of this research was to develop an orally disintegrating tablet (ODT) dosage form containing taste-masked beads of clindamycin HCl. Several formulation strategies were evaluated and a taste-masked ODT of clindamycin HCl was prepared without the use of a waxy cushioning agent. Clindamycin HCl (ca. 46% w/w) was coated onto microcrystalline cellulose beads (Cellets® 200) followed by the addition of a taste-masking layer of amino methacrylate copolymer, NF (Eudragit EPO® (EPO)) coating suspension. The efficiency of both the drug coating process and the taste-masking polymer coating process, as well as the taste masking ODTs was determined using potency and drug release analysis. Magnesium stearate was found to be advantageous over talc in improving the efficiency of the EPO coating suspension. A response surface methodology using a Box–Behnken design for the tablets revealed compression force and levels of both disintegrant and talc to be the main factors influencing the ODT properties. Blending of talc to the EPO-coated beads was found to be the most critical factor in ensuring that ODTs disintegrate within 30?s. The optimized ODTs formulation also showed negligible (<0.5%) drug release in 1?min using phosphate buffer, pH 6.8 (which is analogous to the residence time and pH in the oral cavity). By carefully adjusting the levels of coating polymers, the amounts of disintegrant and talc, as well as the compression force, robust ODTs can be obtained to improve pediatric and geriatric patient compliance for clindamycin oral dosage forms.     

Fast relief from migraine attacks using fast-disintegrating sublingual zolmitriptan tablets

Zolmitriptan is a potent molecule for treatment of migraine. Its current oral therapies present drawbacks such as slow onset of action, low bioavailability and large inter-subject variability. Fast disintegrating sublingual zolmitriptan tablet (FDST) using freeze-drying technique has been developed to enhance tablet disintegration and dissolution with the intention of speeding drug absorption and onset of effect, hence mitigating the effects on the gastrointestinal dysmotility that typically accompanies the migraine attack. The FDSTs were prepared using different concentrations of gelatin as binder and mannitol or L-alanine as matrix supporting/disintegration enhancing agents. The effect of formulation variables on the physicochemical and solid-state properties, as well as the dissolution behaviour of the tablets, was studied. The formulated FDSTs disintegrated within 30 s and showed significantly faster dissolution rate of zolmitriptan compared to the zolmitriptan oral tablet. Tablet containing 2% gelatin and mannitol showed acceptable weight variation, drug content and friability values. Furthermore, it had a low in-vitro and in-vivo disintegration time (11 s) and it reached 100% of drug release within 30 s. This sublingual formulation gave faster and higher zolmitriptan plasma concentration in rabbits compared to the oral zolmetriptan market product. Zolmitriptan FDST may therefore constitute an advance in the management of acute migraine attacks.     

Prelimnaky Evaluation of Cissus Root Gum as a Binder in Sodium Salicylate Tablet Formulations

Abstract

Cissus root gum was processed and evaluated as a binder in lactose-based tablets each containing 100 mg of sodium salicylate as the active ingredient. Acacia binder was used as basis for comparison. Tablet hardness, friability, disintegration time and dissolution rate were the parameters investigated. The cissus gum gave hard and non-friable tablets at 1 - 3% w/w concentration of the tablet formula. Tablets containing above 2% w/w of the cissus gum gave high disintegration time values and the pattern of dissolution of the incorporated drug suggests that the gum may be useful in prolonged release tablet formulations. No significant changes in the tablet properties was observed after storage at 30°C for 16 weeks.     

Effect of crospovidone and hydroxypropyl cellulose on carbamazepine in high-dose tablet formulation

The aim of this study was to develop a high-dose tablet formulation of the poorly soluble carbamazepine (CBZ) with sufficient tablet hardness and immediate drug release. A further aim was to investigate the influence of various commercial CBZ raw materials on the optimized tablet formulation.

Materials and methods: Hydroxypropyl cellulose (HPC-SL) was selected as a dry binder and crospovidone (CrosPVP) as a superdisintegrant. A direct compacted tablet formulation of 70% CBZ was optimized by a 3² full factorial design with two input variables, HPC (0–10%) and CrosPVP (0–5%). Response variables included disintegration time, amount of drug released at 15 and 60?min, and tablet hardness, all analyzed according to USP 31.

Results and discussion: Increasing HPC-SL together with CrosPVP not only increased tablet hardness but also reduced disintegration time. Optimal condition was achieved in the range of 5–9% HPC and 3–5% CrosPVP, where tablet properties were at least 70 N tablet hardness, less than 1?min disintegration, and within the USP requirements for drug release. Testing the optimized formulation with four different commercial CBZ samples, their variability was still observed. Nonetheless, all formulations conformed to the USP specifications.

Conclusions: With the excipients CrosPVP and HPC-SL an immediate release tablet formulation was successfully formulated for high-dose CBZ of various commercial sources.     

Design and in vitro characterization of buccoadhesive tablets of timolol maleate

Objective: The purpose of this work was to develop and evaluate buccoadhesive tablets of timolol maleate (TM) due to its potential to circumvent the first-pass metabolism and to improve its bioavailability.

Methods: The tablets were prepared by direct compression using two release modifying polymers, Carbopol 974P (Cp-974p) and sodium alginate (SA). A 3² full factorial design was employed to study the effect of independent variables, Cp-974p and SA, in various proportions in percent w/w, which influences the in vitro drug release and bioadhesive strengths. Physicochemical properties of the drug were evaluated by ultraviolet, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (P-XRD). Tablets were evaluated for hardness, thickness, weight variation, drug content, surface pH, swelling index, bioadhesive force and in vitro drug release.

Results: The FTIR and DSC studies showed no evidence of interactions between drug, polymers and excipients. The P-XRD study revealed that crystallinity of TM remain unchanged in optimized formulation tablet. Formulation F9 achieves an in vitro drug release of 98.967%?±?0.28 at 8?h and a bioadhesive force of 0.088 N?±?0.01211.

Conclusion: We successfully developed buccal tablet formulations of TM and describe a non-Fickian-type anomalous transport as the release mechanism.     

Development of self-microemulsifying drug delivery system for oral bioavailability enhancement of berberine hydrochloride

The purpose of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to improve the oral bioavailability of Berberine hydrochloride (BBH), an important bioactive compound from Chinese Medicines with poor water solubility. Pseudoternary phase diagrams were constructed using oil, surfactant and co-surfactant types to identify the efficient self-microemulsification region. SMEDDS was characterized by morphological observation, droplet size, zeta-potential determination, stability, in vitro release and in vivo bioavailability study. The optimal formulation with the best self-microemulsifying and solubilization ability consisted of 40% (w/w) of ethyl linoleate and oleic acid (2:1), 35% (w/w) Tween-80 and 25% (w/w) glycerol. The SMEDDS of BBH could exhibit good stability. In vitro release test showed a complete release of BBH from SMEDDS was in 5 h. In vivo results indicated that the peak plasma concentration (C_max) and the area under the curve (AUC_{0→12 h}) of SMEDDS of BBH were higher than the commercial tablet by 163.4% and 154.2%, respectively. The relative bioavailability of SMEDDS of BBH was enhanced about 2.42-fold compared with the commercial tablet in rats. The study confirmed that the SMEDDS formulation could be used as a possible alternative to traditional oral formulations of BBH to improve its bioavailability.     

Dextrose monohydrate as a non-animal sourced alternative diluent in high shear wet granulation tablet formulations

The feasibility of dextrose monohydrate as a non-animal sourced diluent in high shear wet granulation (HSWG) tablet formulations was determined. Impacts of granulation solution amount and addition time, wet massing time, impeller speed, powder and solution binder, and dry milling speed and screen opening size on granule size, friability and density, and tablet solid fraction (SF) and tensile strength (TS) were evaluated. The stability of theophylline tablets TS, disintegration time (DT) and in vitro dissolution were also studied. Following post-granulation drying at 60?°C, dextrose monohydrate lost 9% water and converted into the anhydrate form. Higher granulation solution amounts and faster addition, faster impeller speeds, and solution binder produced larger, denser and stronger (less friable) granules. All granules were compressed into tablets with acceptable TS. Contrary to what is normally observed, denser and larger granules (at ≥21% water level) produced tablets with a higher TS. The TS of the weakest tablets increased the most after storage at both 25?°C/60% RH and 40?°C/75% RH. Tablet DT was higher for stronger granules and after storage. Tablet dissolution profiles for 21% or less water were comparable and did not change on stability. However, the dissolution profile for tablets prepared with 24% water was slower initially and continued to decrease on stability. The results indicate a granulation water amount of not more than 21% is required to achieve acceptable tablet properties. This study clearly demonstrated the utility of dextrose monohydrate as a non-animal sourced diluent in a HSWG tablet formulation.     

Development of Sustained-Release Tablets Containing Sodium Valproate: In Vitro and In Vivo Correlation

ABSTRACT

We have developed a 200 mg and 400 mg sustained-release sodium valproate tablet that allows effective blood concentration of the active drug with once-a-day dosing. The controlled dissolution or sustained release of the drug was attained by a membrane-controlled system. A single-coating system did not adequately control the dissolution rate, and therefore double-coated tablets were prepared and a human pharmacokinetic study was conducted. With the 200 mg VPA-Na tablets, the nonfasting C_max was only 20% higher than the fasting C_max. An in vitro dissolution test was conducted to predict the effects of food on drug dissolution after administration of this tablet. A relatively good correlation was observed between the absorption profiles and the dissolution profiles of the drug.     

Comparative study of different approaches for preparation of chlorzoxazone orodispersible tablets

Abstract

Context: Muscle spasm is a painful involuntary contraction of muscles, which causes involuntary movement and distortion. Chlorzoxazone is a centrally acting muscle-relaxant with sedative properties, but given orally, it is hepatically metabolized leading to decreased bioavailability.

Objective: Orodispersible tablets (ODTs) of chlorzoxazone were formulated using two different approaches; by coprocessed excipients (CE) or by liquisolid (LS) technique.

Materials and methods: Pharmaburst^® 500, Starlac^®, Pearlitol flash^®, Prosolv^® odt and F-melt^® were used as coprocessed superdisintegrants, whereas in LS, Avicel^® PH101, Microcelac^® 100 and Cellactose^® 80 were used as carriers, while Aerosil^® 200 was the coating material. ODTs were evaluated in terms of weight and thickness variations, drug content, hardness, friability, wetting time, dissolution, disintegration time (DT) and palatability.

Results: In vitro DT of CE-ODTs ranged from 26.43?±?1.693?s to >180?s, whereas it was between 25.42±?0.203?s to >180?s in LS-ODTs. Complete drug release within 15?min was attained by CE1 prepared with 92.5?mg Pharmaburst^® 500. In vivo DT of CE1 and LS3 were 19.779?±?0.810 and 18.105?±?0.423?s, respectively, using six volunteers. Volunteers found that CE1 had more acceptable taste and was more palatable than LS3.

Conclusion: It was concluded that chlorzoxazone ODTs could be successfully formulated using either CE or LS techniques and be used as novel dosage forms for pediatrics and geriatrics showing improved drug release. Moreover, CE technique was superior to LS technique in terms of palatability.     

Formulation and in vitro evaluation of a thermoreversible mucoadhesive nasal gel of itopride hydrochloride

Itopride hydrochloride (ITO HCl) is a prokinetic agent, used in the treatment of gastrointestinal motility disorders. The aim of the study was to develop stable mucoadhesive thermoreversible nasal gel to avoid first pass effect. ITO HCl was incorporated into the blends of thermoreversible polymers like poloxamer 407 and various mucoadhesive polymers in different concentrations to increase the contact of the formulations with nasal mucosa. The compatibility between the drug and the suggested polymers was studied by Fourier transform infrared and differential scanning calorimetry (DSC). The formulations were evaluated for clarity, pH, gelation temperature, mucoadhesive strength, gel strength, viscosity, and drug content. In addition, the in vitro drug release and the dissolution efficiency (DE)% were measured. The optimized formulations that showed the highest dissolution efficiency% (DE%) in saline phosphate buffer of pH 6.4 at 35?±?0.5?°C were chosen for stability testing at temperatures of 4?±?2 and 25?±?2?°C/60?±?5% RH. It was found that F1 and F17 that contain 18% w/v poloxamer 407 and 0.5% w/v of hydroxypropylmethyl cellulose K4M or methyl cellulose (MC), respectively, showed higher stability results as indicated by their higher t₉₀ values (days).