Prochlorperazine Research Articles

Prochlorperazine maleate versus placebo for the prevention of acute mountain sickness: study protocol for a randomized controlled trial

BackgroundAcute mountain sickness (AMS) is a debilitating condition that individuals may develop on ascent to high altitude. It is characterized by headache, nausea, vomiting, dizziness, and fatigue with the potential to progress to fatal disease. Although the pathophysiology of AMS remains unclear, proposed mechanisms are hypothesized to be similar to migraine. Prochlorperazine, a first-line treatment for acute migraine, has been shown to abort migraine early and thus may be effective in preventing AMS. Its action as a respiratory stimulant additionally makes it a promising novel agent for AMS prevention.MethodsIn this randomized double-blinded trial, participants will be randomized to receive oral prochlorperazine maleate or placebo for 24 h of three times daily dosing on a rapid ascent to 4348 m. Participants will be adults, aged 18, and older who are unacclimatized. Participants will remain at this elevation overnight. The Lake Louise Questionnaire will be utilized to define the primary outcome and presence of AMS and will be assessed the evening of and morning after ascent to peak altitude.DiscussionCurrently, acetazolamide is the preferred option for the chemoprophylaxis of AMS, which has been studied and utilized since the 1970s and involves potential prohibitive side effects. Other more efficacious options with more tolerable side effects are needed. Preventing AMS has the potential to limit both the morbidity and mortality associated with developing AMS and more serious diseases (notably high-altitude cerebral edema). Additionally, there is a substantial economic and environmental impact of AMS that could be prevented.Trial registrationClinicaltrial.gov, NCT06450899. Registered on June 2024.

Sustained Endocytosis Inhibition via Locally-Injected Drug-Eluting Hydrogel Improves ADCC-Mediated Antibody Therapy in Colorectal Cancer.

The epidermal growth factor receptor (EGFR) is a validated therapeutic target for RAS/RAF wild-type colorectal cancer (CRC). However, monoclonal antibody-based anti-EGFR therapies such as cetuximab have limited effectiveness. Herein, it is identified that EGFR internalization is associated with poor treatment response and prognosis in patients with CRC, based on a retrospective analysis of patients treated with cetuximab. It is further demonstrated that the endocytosis inhibitor prochlorperazine (PCZ) can move EGFR, which is hidden inside the cell, to the cell surface to improve therapeutic antibody binding. Thus, a thermosensitive hydrogel co-loaded with cetuximab and PCZ (Gel@Cmab/PCZ) is constructed for sustained inhibition of endocytosis and effective cetuximab delivery. Peritumoral injection of Gel@Cmab/PCZ shows strong antitumor efficacy in subcutaneous and orthotopic CRC tumor models and completely abrogated liver metastasis when combined with chemotherapy. In a humanized patient-derived xenograft model, a single injection of Gel@Cmab/PCZ with one-third of theconventional cetuximab dose achieved 91% tumor growth inhibition, which promoted NK cell infiltration into tumor tissues and their antibody-dependent cell-mediated cytotoxicity effect. This study represents a novel strategy to boost the monoclonal antibody-mediated anti-tumor response in CRC.

Quantification of the interaction forces between dengue virus and dopamine type-2 receptor using optical tweezers

BackgroundDengue virus (DENV) causes the most significant mosquito-borne viral disease with a wide spectrum of clinical manifestation, including neurological symptoms associated with lethal dengue diseases. Dopamine receptors are expressed in central nervous system, and dopamine antagonists have been reported to exhibit antiviral activity against DENV infection in vivo and in vitro. Although identification of host-cell receptor is critical to understand dengue neuropathogenesis and neurotropism, the involvement of dopamine receptors in DENV infection remains unclear.ResultsWe exploited the sensitivity and precision of force spectroscopy to address whether dopamine type-2 receptors (D2R) directly interact with DENV particles at the first step of infection. Using optical tweezers, we quantified and characterized DENV binding to D2R expressed on Chinese hamster ovary (CHO) cells. Our finding suggested that the binding was D2R- and DENV-dependent, and that the binding force was in the range of 50–60 pN. We showed that dopamine antagonists prochlorperazine (PCZ) and trifluoperazine (TFP), previously reported to inhibit dengue infection, interrupt the DENV-D2R specific binding.ConclusionsThis study demonstrates that D2R could specifically recognize DENV particles and function as an attachment factor on cell surfaces for DENV. We propose D2R as a host receptor for DENV and as a potential therapeutic target for anti-DENV drugs.Graphical abstract

Synthesis and Structure of Novel Phenothiazine Derivatives, and Compound Prioritization via In Silico Target Search and Screening for Cytotoxic and Cholinesterase Modulatory Activities in Liver Cancer Cells and In Vivo in Zebrafish.

Phenothiazines (PTZ) are antipsychotics known to modulate a variety of neurotransmitter activities that include dopaminergic and cholinergic signaling and have been identified as potential anticancer agents in vitro. However, it is important to also test whether a highly cytotoxic, repurposed, or novel PTZ has low toxicity and neuromodulatory activity in vivo using vertebrate model organisms, such as zebrafish. In this study, we synthesized novel phenothiazines and screened them in vitro in liver cancer and in vivo in zebrafish embryos/larvae. The syntheses of several intermediate PTZ 10-yl acyl chlorides were followed by elemental analysis and determination of 1H NMR and 13C NMR mass (ESI+) spectra of a large number of novel PTZ 10-carboxamides. Cytotoxicities of 28 PTZ derivatives (1-28) screened against Hep3B and SkHep1 liver cancer cell lines revealed five intermediate and five novel leads along with trifluoperazine (TFP), prochlorperazine (PCP), and perphenazine, which are relatively more cytotoxic than the basic PTZ core. Overall, the derivatives were more cytotoxic to Hep3B than SkHep1 cells. Moreover, in silico target screening identified cholinesterases as some of the commonest targets of the screened phenothiazines. Interestingly, molecular docking studies with acetylcholinesterase (AChE) and butyrylcholinesterase proteins showed that the most cytotoxic compounds 1, 3, PCP, and TFP behaved similar to Huprin W in their amino acid interactions with the AChE protein. The highly cytotoxic intermediate PTZ derivative 1 exhibited a relatively lower toxicity profile than those of 2 and 3 during the zebrafish development. It also modulated in vivo the cholinesterase activity in a dose-dependent manner while significantly increasing the total cholinesterase activity and/or ACHE mRNA levels, independent of the liver cancer cell type. Our screen also identified novel phenothiazines, i.e., 8 and 10, with significant cytotoxic and cholinesterase modulatory effects in liver cancer cells; yet both compounds had low levels of toxicity in zebrafish. Moreover, they modulated the cholinesterase activity or expression of ACHE in a cancer cell line-specific manner, and compound 10 significantly inhibited the cholinesterase activity in zebrafish. Accordingly, using a successful combination of in silico, in vitro, and in vivo approaches, we identified several lead anticancer and cholinesterase modulatory PTZ derivatives for future research.

FORMULATION AND EVALUATION OF ORODISPERSIBLE TABLET OF PROCHLORPERAZINE MALEATE

In the present work, fast disintegrating tablets of prochlorperazine maleate were designed with a view to enhance patient compliance by effervescent method. Prochlorperazine Maleate, a potent antipsychotic medication with antiemetic properties, holds significance in treating various conditions such as nausea, vomiting, and vertigo. The decision to formulate it into orodispersible tablets aimed to address issues related to patient compliance and convenience, particularly for individuals who experience difficulty swallowing conventional tablets. Formulation F10, enriched with 10% Croscarmellose sodium as a superdisintegrant and an effervescent mixture for taste masking, exhibited remarkable characteristics. Croscarmellose sodium, chosen for its exceptional disintegration properties, ensures rapid breakdown upon contact with saliva, facilitating swift drug release and subsequent onset of action. Moreover, the incorporation of an effervescent mixture not only aids in masking the potentially unpleasant taste of Prochlorperazine Maleate but also holds the potential to enhance palatability and overall patient acceptance. Physicochemical characterization of Prochlorperazine Maleate unveiled favorable attributes, including a loss on drying of 0.413±0.002%, a melting point range of 234-236°C, and a moisture content of 0.0354%, affirming its suitability for formulation into orodispersible tablets. Through dissolution profile comparisons, formulation F10 demonstrated superior drug release kinetics compared to the commercial formulation, underscoring its potential therapeutic advantages.

A PEGylated liposomal formulation of prochlorperazine that limits brain exposure but retains dynamin II activity: A potential adjuvant therapy for cancer patients receiving chemotherapeutic mAbs

Anti-cancer monoclonal antibodies often fail to provide therapeutic benefit in receptor-positive patients due to rapid endocytosis of antibody-bound cell surface receptors. High dose co-administration of prochlorperazine (PCZ) inhibits endocytosis and sensitises tumours to mAbs by inhibiting dynamin II but can also introduce neurological side effects. We examined the potential to use PEGylated liposomal formulations of PCZ (LPCZ) to retain the anti-cancer effects of PCZ, but limit brain uptake. Uncharged liposomes showed complete drug encapsulation and pH-dependent drug release, but cationic liposomes showed limited drug encapsulation and lacked pH-dependent drug release. Uncharged LPCZ showed comparable inhibition of EGFR internalisation to free PCZ in KJD cells. After IV administration to rats, LPCZ reduced the plasma clearance and brain uptake of PCZ compared to IV PCZ. The results suggest that LPCZ may offer some benefit over PCZ as an adjunct therapy in cancer patients receiving mAb treatment.

The Application of Response Surface Methodology (RSM) In the Computational Optimization of Sustained Release (SR) For Phenothiazine Derivative Matrix Tablet

Introduction: This study explores the use of Response Surface Methodology (RSM), a statistical optimization technique, to optimize the SR properties of prochlorperazine maleate (PCM) matrix tablets. PCM is a phenothiazine derivative used for treating schizophrenia, nausea, and vomiting. Sustained-release formulations offer extended drug delivery, potentially improving patient compliance and reducing side effects. RSM helps identify optimal combinations of critical formulation factors influencing drug release, such as polymer type and concentration, filler type, and drug/polymer ratio. The study likely involves designing experiments based on chosen RSM designs (e.g., Box-Behnken) with varying factor levels. Formulate SR tablets with different factor combinations. Evaluating the drug release profiles of each tablet formulation. Analyzing data using RSM software to build mathematical models relating factors to drug release and identifying optimal factor combinations that maximize desired release characteristics. Objective: The ongoing research purpose to improve the advancement of a sustained release tablet containing Phenothiazine derivative PCM loaded matrix. This is achieved by utilizing DoE as a computational method to statistically validate the formulation. Methodology: Basically two methods involved in the formulation using direct compression; a simple and efficient method where all dry ingredients are blended and directly compressed into tablets. Results: The obtained outcomes closely matched the anticipated values derived from the experimental setup. The enhanced PCM matrix tablets demonstrated a prolonged and uniform discharge of PCM over a span of 6 hours. Conclusion: This study Based on a 23 FD, response surface methodology was used to successfully develop the current research of PCM matrix tablets for sustained release application. The corresponding contour plots and 3D response methodology represent the important variables for the optimisation process.

Dose-Dependent Effect of Phenothiazines as Dynamin II Inhibitors on the Uptake of PEGylated Liposomes by Endocytic Cells and In Vivo Pharmacokinetics of PEGylated Liposomal Doxorubicin in Rats.

Dynamin II (dynII) plays a significant role in the internalization pathways of endocytic cells, by allowing membrane invaginations to "bud off". An important class of dynII inhibitors that are used clinically are phenothiazines, such as prochlorperazine (PCZ). PCZ is an antipsychotic drug but is also currently in clinical trials at higher concentrations as an adjuvant in cancer patients that increases the efficacy of monoclonal antibodies at high intravenous doses. It is unknown, however, whether high-dose dynII inhibitors have the potential to alter the pharmacokinetics of co-administered chemotherapeutic nanomedicines that are largely cleared via the mononuclear phagocyte system. This work therefore sought to investigate the impact of clinically relevant concentrations of phenothiazines, PCZ and thioridazine, on in vitro liposome endocytosis and in vivo liposome pharmacokinetics after PCZ infusion in rats. The uptake of fluorescently labeled PEGylated liposomes into differentiated and undifferentiated THP-1 and RAW246.7 cells, and primary human peripheral white blood cells, was investigated via flow cytometry after co-incubation with dynII inhibitors. The IV pharmacokinetics of PEGylated liposomes were also investigated in rats after a 20 min infusion with PCZ. Phenothiazines and dyngo4a reduced the uptake of PEGylated liposomes by THP-1 and RAW264.7 cells in a concentration-dependent manner in vitro. However, dynII inhibitors did not alter the mean uptake of liposomes by human peripheral white blood cells, but endocytic white cells from some donors exhibited sensitivity to phenothiazine exposure. When a clinically relevant dose of PCZ was co-administered with PEGylated liposomal doxorubicin (Caelyx/Doxil) in rats, the pharmacokinetics and biodistribution of liposomes were unaltered. These data suggest that while clinically relevant doses of dynII inhibitors can inhibit the uptake of liposomes by endocytic cells in vitro, they are unlikely to significantly affect the pharmacokinetics of long-circulating, co-administered liposomes.

G4-binding drugs, chlorpromazine and prochlorperazine, repurposed against COVID-19 infection in hamsters.

The COVID-19 pandemic caused by SARS-CoV-2 has caused millions of infections and deaths worldwide. Limited treatment options and the threat from emerging variants underline the need for novel and widely accessible therapeutics. G-quadruplexes (G4s) are nucleic acid secondary structures known to affect many cellular processes including viral replication and transcription. We identified heretofore not reported G4s with remarkably low mutation frequency across >5 million SARS-CoV-2 genomes. The G4 structure was targeted using FDA-approved drugs that can bind G4s - Chlorpromazine (CPZ) and Prochlorperazine (PCZ). We found significant inhibition in lung pathology and lung viral load of SARS-CoV-2 challenged hamsters when treated with CPZ or PCZ that was comparable to the widely used antiviral drug Remdesivir. In support, in vitro G4 binding, inhibition of reverse transcription from RNA isolated from COVID-infected humans, and attenuated viral replication and infectivity in Vero cell cultures were clear in case of both CPZ and PCZ. Apart from the wide accessibility of CPZ/PCZ, targeting relatively invariant nucleic acid structures poses an attractive strategy against viruses like SARS-CoV-2, which spread fast and accumulate mutations quickly.

Development of Fast Dissolving Buccal Patches of Prochlorperazine Maleate for Effective Management of Emesis

The goal of this research was to increase the oral bioavailability and avoid the first pass metabolism of Prochlorperazine Maleate (used to treat nausea and vomiting) by creating its buccal patches. Prochlorperazine is a member of BCS II and has an oral bioavailability of 11– 15%. Prochlorperazine maleate buccal patches were made by solvent casting with the aid of HPMC E-15 and Chitosan (film-forming agents), Glycerol (plasticizer), Tween 80 (penetration enhancer), Citric Acid (saliva stimulating agent), Mannitol (sweetening agent), and Ethyl Cellulose (Backing membrane). Twelve total formulations was made by using different quantities of polymers and formulation was evaluated for weight variation, thickness, folding endurance, drug content, in- vitro diffusion, in vitro, bio-adhesion time, percent moisture loss, % swelling index and stability study. Based on results it was concluded that buccal patches (F4) showed enhanced bioavailability. Keywords: Prochlorperazine maleate, Buccal Patches, Bioavailability, Stability

Development and Validation of Prochlorperazine Maleate in Bulk and Pharmaceutical Dosage Form by UV Spectroscopic Method

Objectives: Prochlorperazine maleate is an antipsychotic and antiemetic drug that is available as tablets on the market for oral administration. The main object of this research work is to develop and validate the easiest UV spectroscopic method for the determination of Prochlorperazine maleate for tablet formulation (marketed formulation). Materials and Methods: A simple, reproducible and efficient method for the determination of Prochlorperazine maleate in bulk and tablet formulations have been developed. The developed method is based on the estimation by UVVisible spectroscopy. In this method, 0.3M HCL was selected as the solvent. A Wavelength selected for estimation of Prochlorperazine maleate was 254 nm. Results: Linearity was found in the concentration range 2-16μg/ml (R2=0.9909). A recovery study was found to be 98.01-99.79% for Prochlorperazine maleate. The method was found to be precise as % RSD was low in repeatability, intermediate precision, and reproducibility. LOD and LOQ were found to be 0.58 and 1.75 respectively. Conclusion: The method was found to be very simple, and precise. It also had a good recovery. The Developed method can be used for further routine analysis and stability study of a Prochlorperazine maleate.

Development of Optimized Sumatriptan-Prochlorperazine Combined Orodispersible Films Without Disintegrant: in vitro, ex vivo and in vivo Characterization.

Sumatriptan succinate and prochlorperazine maleate are a clinically proven combination for treating migraine and associated nausea and vomiting. Classical oral dosage forms are not frequently workable in migraine because of the associated nausea/vomiting, and no effectivefixed dose combination is available. Thus, the aim of the study was to optimize a combined sumatriptan-prochlorperazine orodispersible film for rapid release of drugs. Orodispersible films were prepared by solvent casting method using varied amounts of polyvinyl alcohol and glycerol as film former and plasticizer, respectively, along with fixed levels of other ingredients employing central composite design. The optimum film (VF) demonstrated disintegration and total dispersion times as 21 s and 2.3 min, respectively. Tensile strength and Young's modulus were 8.86 ± 0.37 MPa and 24.15 ± 0.07 MPa, respectively. The in vitro T80% of both drugs from the ODF was achieved within 4 min. The film was palatable and disintegrated in 2 min in buccal cavity of human volunteers. Permeation study through goat mucosa demonstrated 100% permeation of both drugs within 15 min. X-Ray diffraction and differential scanning calorimetry supported drugs being amorphous and Fourier transform infrared demonstrated drug-excipient compatibility in optimized film. A judicious combination of sumatriptan succinate and prochlorperazine maleate could be prepared in orodispersible films for the possible relief of migraine.

A facile development of rare earth neodymium nickelate nanoparticles for selective electrochemical determination of antipsychotic drug prochlorperazine

In this study, the synthesis of neodymium nickelate (Nd2NiO4, NNO) nanoparticles with diverse temperatures were developed by the simple coprecipitation method. The successfully prepared NNO was characterized with various spectroscopic instruments. The surface morphology, size, shape, composition, crystallinity, functionality, bonding, and the presence of elements of the nanoparticles were analyzed by suitable characterization techniques. The electrochemical features were investigated by electrochemical impedance spectroscopy, cyclic voltammetry, and differential pulse voltammetry (EIS, CV, and DPV) methods. As results expected, the modified NNO-500/SPCE sensor displays low electron transfer resistance (Rct), high active surface area, and excellent electrocatalytic activity for the detection of prochlorperazine (PCP) rather than other electrodes. Under optimized electrochemical detections, the DPV study revealed a low limit of detection (LoD), and limit of quantification (LoQ) of 4 nM, and 14 nM with wide linearity of 0.025–1220 µM for PCP at the NNO-500 sensor. In addition, high selectivity, stability, precision, and satisfactory recoveries in biological samples for PCP detection. Thus, our study provides a simplistic but effective method for constructing perovskite-type materials with excellent electrochemical performance.

Rational design of manganese oxide/tin oxide hybrid nanocomposite based electrochemical sensor for detection of prochlorperazine (Antipsychotic drug)

The development of hybrid metal oxides nanocomposite has been utilized for the electrochemical sensor with low detection limits, and excellent sensitivity. In this present study, the co-precipitation synthesis of manganese oxide/tin oxide (Mn2O3/SnO2) hybrid nanocomposite was developed and applied for prochlorperazine (PCP) electrochemical detection. The structural and morphological properties of the prepared hybrid nanocomposite were characterized with various analytical techniques. The synthesized Mn2O3/SnO2 was modified on a screen-printed carbon electrode (SPCE) surface and utilized cyclic voltammetric (CV) and differential pulse voltammetric (DPV) analysis. The linking advantages of Mn2O3, SnO2, and SPCE show superior electrochemical performance in PCP detection, displaying high oxidation response than that of the unmodified SPCE and other modified electrodes (Mn2O3 and SnO2). The optimized voltammetric results exhibited that the hybrid modified electrode shows a broad linear range of 0.03–421.45 µM, the lowest limit of detection, and the limit of quantification of 8 nM, and 29 nM with high sensitivity of 1.415 µA µM−1 cm−2 for PCP oxidation. Besides, the constructed sensor reveals excellent selectivity, stability, and precision for the detection of PCP. Finally, the viability of the hybrid sensor was performed to PCP determination in real human samples with satisfactory results.

Prochlorperazine enhances radiosensitivity of non-small cell lung carcinoma by stabilizing GDP-bound mutant KRAS conformation

Lung cancer is considered as leading cancer with the highest mortality. The KRAS-oncogenic mutations are dominant in lung carcinoma leading to poor prognosis and radioresistance, which is a major impediment to radiotherapy. Thus, KRAS mutant inhibitors that synergistically sensitize tumours to radiation are urgently needed. In pursuance of the search for a novel radiosensitizer, high-throughput screening of FDA-approved drugs was performed at active site of K-Ras. Prochlorperazine (PCZ), an antipsychotic drug, showed good binding affinity with KRAS-mutant proteins. PCZ binds to the GTP-binding pocket of KRAS-mutant protein and inhibits its constitutive activation by stabilizing the GDP-bound conformation of K-Ras mutants by 9 kcal/mol compared to WT. PCZ alongwith radiation decreased the clonogenic survival of KRAS-mutant NSCLC but not KRAS-WT cells. The combination treatment activates p-ATM, p53, and p21 proteins, leading to cell cycle arrest. PCZ with increasing radiation caused a linear increase in γH2AX foci, suggesting enhanced DSBs-associated apoptosis in radioresistant A549 cells. Pharmacokinetics study showed Cmax = 526 ng/ml at 30min, 4.6h half-life in plasma, and highest accumulation in tumours. PCZ and 10Gy irradiation synergistically radiosensitize mice xenografts via downregulation of Ras/Raf/MEK/ERK pathway. Our efforts have led to the discovery of PCZ as a lead compound. In preclinical analyses, treatment with PCZ alone and in combination with radiation led to regression of KRAS−G12S tumours.

Solubility and Dissolution Study of Prochlorperazine Maleate Nanoparticle Prepared by Design of Experiment

The objective of the present work was to improve the solubility and dissolution rate of the poorly water-soluble drug, prochlorperazine maleate (PCM), by preparing nanoparticles using wet media milling method. The first screening design (Plackett–Burman) was applied to screen the significant factors among all the factors. Then, final nanoparticles were optimized by Box–Behnken design and evaluated for independent variables viz. the amount of Pluronic F127, amount of PCM, and milling speed on dependent variables such as particle size, saturated solubility, and dissolution efficiency at 5 min. The Pareto chart revealed a significant effect of three variables among all variables (P < 0.001). Based on the desirability (Box–Behnken), formulation containing 0.5 w/v Pluronic F127, 40 mg of PCM, and 571 RPM speed was considered as an optimized batch. DSC and PXRD studies indicated that dissolution enhancement was due to particle size reduction. It was again confirmed by surface electron microscopy. The study proved a significant improvement in the dissolution rate of prochlorperazine maleate by preparing nanoparticles.

Unprecedented High Throughput Titration by Feedback-Based and Subsequent Fixed Triangular Wave-Controlled Flow Ratiometry and Its Application to Quantification of Japanese Pharmacopoeia Drugs

Throughput rate of flow ratiometric titration has further been enhanced by shortening the lag time from the confluence of solutions upstream to the sensing of signal downstream and by optimizing analytical parameters. Feedback-based upward and downward scans of titrand/titrant flow ratio were repeated in order to offset the effect of the lag time and thus to locate the equivalence point. Subsequent faster fixed triangular wave-controlled scans in narrower range further increased the throughput rate. Analytical parameters such as scan rate and scan range were optimized. Maximally, 46.9 titrations/min was realized with reasonable precision (RSD = 1.79%). Applicability of the method to the quantitation of the Japanese Pharmacopoeia drugs (furosemide, isoniazid and prochlorperazine maleate) was verified, where the latter two drugs were determined by nonaqueous titrations.

\u201cPhantom akathisia\u201d in an amputated leg of a sarcoma patient: a case report

BackgroundAkathisia is a rather common extrapyramidal side effect of antipsychotic drugs and antidepressants, often resulting in severe discomfort for patients. However, due to the diversity of symptoms, it is often overlooked. We hereby report a case with akathisia that mainly appeared in an amputated leg.Case presentationsA 60-year-old woman, who had undergone external hemipelvectomy for a recurrent soft tissue sarcoma, was referred to the Department of Psycho-Oncology due to worsening anxiety and restlessness. She was not unconscious or disoriented. Her chief complains included restlessness, an itching sensation in the area corresponding to the amputated left leg, and a feeling as if the lost left leg were raising itself. Detailed examination revealed that she had been administered 10 mg per day of oral prochlorperazine maleate for nausea induced by the oxycodone that had been prescribed to control post-operative pain. Akathisia was suspected and prochlorperazine maleate treatment was discontinued. All the symptoms were alleviated on the next day, and disappeared in 3 days. Eventually, she was diagnosed with akathisia.ConclusionsThis case indicates that the symptoms associated with akathisia can occur in an amputated extremity. Considering two previous reports of “phantom dyskinesia”, extrapyramidal syndromes may result in unusual presentations if occurring in an amputated extremity. Not only should the use of antipsychotic drugs and antidepressants be carefully considered, but also closer observation of psychological symptoms is required after prescription of these drugs because the clinical presentation of akathisia can be various and confusing due to modifications caused by other factors as in this case.

The Oxidative Derivatization Method For The Indirect Spectrophotometric Determination Of Prochlorperazine In Tablets

The oxidative derivatization method by means of peroxoacid for the indirect spectrophotometric determination of Prochlorperazine Maleate is presented. Potassium hydrogen peroxymonosulfate as a derivatizing agent, yielding the Prochlorperazine sulfoxide with λmaх=338 nm is proposed. This reaction product was successfully employed for the spectrophotometric determination of the Prochlorperazine Maleate. The UV spectrophotometric determination of Prochlorperazinе as its sulfoxide proved to be the more robust and selective method. Concentration dependence of the oxidation product remains linear in the range of concentrations from 2 to 40 μg∙mL-1. Limit of quantification (LOQ) is 1.7 μg·mL-1. A new spectrophotometric technique was developed and the possibility of quantitative determination of Prochlorperazine Maleate in 5 mg Vetrinex tablets was demonstrated. The present method is precise and accurate. The common excipients employed do not interfere in the determination. Results of analysis of the tablet dosage form by the proposed method are in good agreement with those of the official method. RSD = 1.34 % (δ = ± 0.57 %).

Formulation and Evaluation of Mouth Dissolving Film of Prochlorperazine Maleate

This research work was aimed to enhance the oral bioavailability and provide faster onset of action of Prochlorperazine maleate (used for the treatment nausea and vomiting) by formulating its mouth dissolving film (MDF). Prochlorperazine belongs to BCS II and oral bioavailability of it’s about 11-15%. The MDF of Prochlorperazine maleate was prepared by solvent casting method using HPMC (film forming agent),Glycerol (plasticizer), Betacyclodextrin (solubilizing agent), Citric acid (saliva stimulating agent), Mannitol (sweetening agent). The formulation was optimized by two factors, three levels (32) was used for the formulation optimization of fast dissolving film of Prochlorperazine maleate and experimental trials are performed on all 9 formulation. In which the amount of HPMC, Glycerol were selected as independent variables (factor) varied at three different level: low (-1), medium (0), and high (+1) levels. The drug release and disintegration time used as dependent variables (response). and formulation was evaluated for weight variation, thickness, folding endurance, drug content, in- vitro disintegration, in vitro dissolution study and stability study. Based on results it was concluded that MDF (F3) showed enhanced bioavailability and faster onset of action.&#x0D; Keywords: Prochlorperazine maleate, Mouth dissolving film, bioavailability