A novel nanozyme doped ZnO/r-GO-based sensor for highly sensitive electrochemical determination of muscle-relaxant drug: cyclobenzaprine HCl.

A nanocomposite of Ce-doped ZnO/r-GO was synthesized using a conventional hydrothermal method. The synthesized nanocomposites were utilized for the purpose of sensitive and selective detection of cyclobenzaprine hydrochloride (CBP). The properties of the composite were extensively analyzed, including its morphology, structure, and electrochemical behavior. This study investigates the application of a modified glassy carbon electrode for the detection of CBP, a muscle relaxant used to treat musculoskeletal diseases that cause muscle spasms. The electrode is modified with Ce-doped ZnO/r-GO. Various detection methods, such as cyclic voltammetric and square wave techniques (SWV), were utilized. The composite material showed high effectiveness as an electron transfer mediator in the oxidation of CBP. The electrode showed a good response for SWV evaluations in CBP identification, with a minimum detection limit of 1.6 × 10-8 M and a wide linear range from 10 × 10-6 M to 0.6 × 10-7 M, under ideal conditions. The rate constant for charge transfer (ks) and the estimation of the electrochemical active surface area were obtained. A developed sensor exhibited desirable selectivity, long-lasting stability, and remarkable reproducibility. A sensor was used to analyze water, human serum, and urine samples, resulting in positive recovery results.

Development and Quality evaluation of sustained release pellets of eperisone HCl.

The objective was to develop eperisone HCl sustained-release pellets through extrusion spheronization technique and to determine the influence of different hydrophobic (polymeric based and wax-based) and hydrophilic (polymeric based) matrix former on the release of eperisone HCl (BCS class I drug) and on pellet sphericity. The pellet formulations consisted of different hydrophobic and hydrophilic matrix formers like HPMC K4M (10-20%) HPMC K15M (10%), EC (7cps) (10-20%), Carnauba wax (10-20%), Compritol ATO 888 (10-20%), Glyceryl monostearate (10%), lactose and microcrystalline cellulose. The initial burst release of the drug from matrix pellet formulations was effectively controlled by coating with 5% EC (ethylcellulose) dispersion. The dissolution profile and drug release kinetics of coated pellet formulations were determined at both acidic and basic pH medium. SEM (Scanning electron microscope) technique was used to determine the surface morphology and cross-section of F5 and F7 pellet formulation. The mechanism of drug release of coated formulation followed non-Fickian diffusion. FTIR spectroscopy was conducted and no drug and excipients interaction was observed. The results had shown that optimized coated formulation was F5 and F7 which effectively extend the drug release for 12 hours.

Selective acetylcholinesterase inhibitors derived from muscle relaxant dantrolene.

Dantrolene, the only therapeutic agent for malignant hyperthermia, is known to have not only a muscle relaxant effect, but also a neuroprotective effect and Alzheimer's disease improving effect. Recently, it has been reported that dantrolene has a weak inhibitory effect on acetylcholinesterase (AChE), which is a therapeutic drug target for Alzheimer's disease. Thus, we focused on developing of AChE inhibitors with benzylpiperidine/piperazine moieties that are based on the dantrolene skeleton. Several derivatives showed an inhibitory activity. Among them, ortho-nitro derivative 8c showed the most potent inhibitory activity with the IC50 value of 34.2 nM. Furthermore, Lineweaver-Burk plot analysis indicated that 8c is AChE-selective inhibitor, which shows only a weak inhibitory effect on butyrylcholinesterase (BuChE) and a non-competitive inhibition.

3D-Printed Gastroretentive Sustained Release Drug Delivery System by Applying Design of Experiment Approach.

This study aimed to develop a novel oral drug delivery system for gastroretentive sustained drug release by using a capsular device. A capsular device that can control drug release rates from the inner immediate release (IR) tablet while floating in the gastric fluid was fabricated and printed by a fused deposition modeling 3D printer. A commercial IR tablet of baclofen was inserted into the capsular device. The structure of the capsular device was optimized by applying a design of experiment approach to achieve sustained release of a drug while maintaining sufficient buoyancy. The 2-level factorial design was used to identify the optimal sustained release with three control factors: size, number, and height of drug-releasing holes of the capsular device. The drug delivery system was buoyant for more than 24 h and the average time to reach 80% dissolution (T80) was 1.7-6.7 h by varying the control factors. The effects of the different control factors on the response factor, T80, were predicted by using the equation of best fit. Finally, drug delivery systems with predetermined release rates were prepared with a mean prediction error ≤ 15.3%. This approach holds great promise to develop various controlled release drug delivery systems.

Development and Stability Control of Pediatric Oral Tizanidine Hydrochloride Formulations for Hospital Use.

Tizanidine hydrochloride is a centrally acting skeletal muscle relaxant used in the treatment of spasticity. This drug is sold only as tablets or capsules, which highlights the need to develop oral liquid formulations that allow administration to children and adults with impaired swallowing. This study aim was to develop and improve tizanidine hydrochloride liquid formulations from raw material and to evaluate their stability. A stability-indicating high performance liquid chromatography method was validated for two formulations developed. Fifteen formulations were developed containing syrup and fifteen containing sodium carboxymethyl cellulose as vehicles, to select the two most suitable for stability testing. The formulations were prepared in triplicate and placed in amber polyethylene terephthalate and glass bottles, which were stored under three different conditions: at room temperature (15-30°C), under refrigeration (2-8°C), and at 40°C. The physicochemical and microbiological stability of formulations were evaluated, applying high performance liquid chromatography and microbiological count. The studied formulations at 15-30°C, 2-8°C, and 40°C can be used for a period of 70 days, and all parameters are inside of recommended specifications, enough to allow its use in the context for which it was developed, the application in hospital. The formulations developed in this work have simple components to avoid adverse reactions in vulnerable populations. Results of this study could be applied as a reference for hospital use; once it demonstrated the reliability of storage time interval and proper conditions for use.

A network of weak hydrogen bonds in the crystal structure of Tetrazepam.

The crystal structure of tetrazepam, a benzodiazepine derivative formerly used for its muscle relaxant properties, has been solved and found to be monoclinic, space group P21/c, with lattice parameters a=12.7386(7)Å, b=11.3774(7)Å, c=10.3084(7)Å, ß=103.175(5) and Vunit-cell=1454.69(16) Å3 at room temperature (293K) with Z=4 molecules in the unit-cell. A network of weak hydrogen bonds involving aliphatic hydrogen atoms plays an important role in the formation of this structure.

Enantioresolution of (RS)-baclofen by liquid chromatography: A review.

Baclofen is a commonly used racemic drug and has a simple chemical structure in terms of the presence of only one stereogenic center. Since the desirable pharmacological effect is in only one enantiomer, several possibilities exist for the other enantiomer for evaluation of the disposition of the racemic mixture of the drug. This calls for the development of enantioselective analytical methodology. This review summarizes and evaluates different methods of enantioseparation of (RS)-baclofen using both direct and indirect approaches, application of certain chiral reagents and chiral stationary phases (though very expensive). Methods of separation of diastereomers of (RS)-baclofen prepared with different chiral derivatizing reagents (under microwave irradiation at ease and in less time) on reversed-phase achiral columns or via a ligand exchange approach providing high-sensitivity detection by the relatively less expensive methods of TLC and HPLC are discussed. The methods may be helpful for determination of enantiomers in biological samples and in pharmaceutical formulations for control of enantiomeric purity and can be practiced both in analytical laboratories and industry for routine analysis and R&D activities.

Baclofen Solution for Low-Volume Therapeutic Delivery.

OBJECTIVES: Baclofen is a zwitterion molecule where increased ions in the excipient increase the solubility. We developed baclofen in a stable solution similar to cerebrospinal fluid (CSF) without bicarbonate and proteins to improve the solubility of the baclofen and to reduce the potential toxicity to the central nervous system (CNS) and subarachnoid space. The objective is to develop a solution of baclofen wherein baclofen is solubilized in a multivalent physiological ion solution such as artificial cerebrospinal fluid (aCSF) at a concentration from 2 mg/cc to 10 mg/cc. METHODS: First, to determine the solubility of Baclofen in aCSF, solubility was determined at six different pH levels at 37°C, by the addition of aCSF to a known amount of Baclofen. The final concentrations were confirmed by high performance liquid chromatography (HPLC) analysis. Second, the stability of Baclofen at 4 mg/cc investigated in a test manufacturing batch utilizing standard methods of production of 1500 20 cc vials inverted for 18 months at 25°C at 60% humidity. The stability and purity of the baclofen was verified at 18 months by HPLC analysis. RESULTS: Baclofen was initially soluble between pH of 6-8 above 7 mg/cc but fell back to 6.3-5.8 mg/cc level with time. Baclofen produced in vials with inversion were noted to be stable at 4 mg/cc at 18 months with less than 2% breakdown of the baclofen in solution. CONCLUSION: Baclofen is much more soluble in artificial CSF than normal saline. The artificial CSF may also be less toxic to the subarachnoid space than saline.

Solubility and Stability of Baclofen 3 mg/mL Intrathecal Formulation and Its Compatibility With Implantable Programmable Intrathecal Infusion Systems.

BACKGROUND: Commercial baclofen formulations used with infusion pumps are available at therapeutic concentrations of 0.5-2.0 mg/mL. However, patients who receive higher daily doses of baclofen may benefit from products with greater baclofen concentrations since their refill frequency would be reduced (up to a maximum of 180 days). We evaluated baclofen solubility, baclofen 3 mg/mL intrathecal (IT) formulation stability, and chemical and physical compatibility with Medtronic SynchroMed® II and Codman Medstream® programmable IT infusion pumps. METHODS: For solubility evaluations, baclofen powder was dissolved into isotonic saline and tested at 5°C, 25°C, and 40°C. To demonstrate drug product stability, both physical and chemical stability attributes of baclofen 3 mg/mL in prefilled syringes were evaluated over 36 months with storage at 25°C. For a simulated in-use stability (compatibility) study, a 3 mg/mL baclofen IT formulation was placed in SynchroMed II and Codman Medstream pumps at 37ºC for study durations, and evaluated at different flow rates. Pump effluent was collected at various times and analyzed by high-performance liquid chromatography for baclofen content. On completion of the in-use stability study, pumps exposed to baclofen 3 mg/mL were dissected and visually evaluated for signs of deterioration. RESULTS: Baclofen solubility was found to be 3.2 mg/mL at 5°C, 3.6 mg/mL at 25°C, and 3.9 mg/mL at 40°C. During the 36-month stability study of prefilled syringes stored at 25°C, baclofen content remained unchanged and no precipitation was observed. The simulated in-use pump study performed at 37ºC showed that a baclofen 3 mg/mL IT formulation was stable at different flow rates and throughout different expected residence times for both pump models. Components from both pumps exhibited no noticeable deterioration after exposure to the 3 mg/mL formulation. CONCLUSION: Baclofen 3 mg/mL IT formulation was stable during long-term storage at 25°C and remained stable under conditions matching those encountered in clinical practice (37°C).

HPLC enantioseparation of racemic bupropion, baclofen and etodolac: modification of conventional ligand exchange approach by pre-column formation of chiral ligand exchange complexes.

Separation of racemic mixture of (RS)-bupropion, (RS)-baclofen and (RS)-etodolac, commonly marketed racemic drugs, has been achieved by modifying the conventional ligand exchange approach. The Cu(II) complexes were first prepared with a few l-amino acids, namely, l-proline, l-histidine, l-phenylalanine and l-tryptophan, and to these was introduced a mixture of the enantiomer pair of (RS)-bupropion, or (RS)-baclofen or (RS)-etodolac. As a result, formation of a pair of diastereomeric complexes occurred by 'chiral ligand exchange' via the competition between the chelating l-amino acid and each of the two enantiomers from a given pair. The diastereomeric mixture formed in the pre-column process was loaded onto HPLC column. Thus, both the phases during chromatographic separation process were achiral (i.e. neither the stationary phase had any chiral structural feature of its own nor did the mobile phase have any chiral additive). Separation of diastereomers was successful using a C18 column and a binary mixture of MeCN and TEAP buffer of pH 4.0 (60:40, v/v) as mobile phase at a flow rate of 1 mL/min and UV detection at 230 nm for (RS)-Bup, 220 nm for (RS)-Bac and 223 nm for (RS)-Etd. Baseline separation of the two enantiomers was obtained with a resolution of 6.63 in <15 min. Copyright © 2016 John Wiley & Sons, Ltd.

[Aqueous and salt solutions of quinine of low concentrations: self-organization, physicochemical properties and actions on the electrical characteristics of neurons].

Self-organization, the physicochemical properties of aqueous and salt solutions of quinine and the effects of salt quinine solutions in a wide range of concentrations (1 x 10(-22) - 1 x 10(-3) M) on the electrical characteristics of the edible snail's identified neurons were studied. Similar non-monotonic concentration dependencies of physicochemical properties of aqueous and salt quinine solutions at low concentrations are obtained. This allows of predicting the occurrence of biological effects at low concentrations of quinine solutions. Intrinsic (within 5% of the interval) changes in membrane potential, the amplitude and duration of the neuron action potential under the influence of quinine salt solutions at concentrations of quinine of 1 x 10(-20), 1 x 10(-18), 1 x 10(-10) M are found. For these concentrations the extreme values of specific conductivity and pH are shown.

Predicting the sites and energies of noncovalent intermolecular interactions using local properties.

Feed-forward artificial neural nets have been used to recognize H-bond donor and acceptor sites on drug-like molecules based on local properties (electron density, molecular electrostatic potential and local ionization energy, electron affinity, and polarizability) calculated at grid points around the molecule. Interaction energies for training were obtained from B97-D and ωB97X-D/aug-cc-pVDZ density-functional theory calculations on a series of model central molecules and H-bond acceptor and donor probes constrained to the grid points used for training. The resulting models provide maps of both classical and unusual H- and halogen-bonding sites. Note that these reactions result even though only classical H-bond donors and acceptors were used as probes around the central molecules. Some examples demonstrate the ability of the models to take the electronics of the central molecule into consideration and to provide semiquantitative estimates of interaction energies at low computational cost.

Three novel benzothiazine-fused triazoles as potential centrally acting muscle relaxants.

The structures of the novel triazolobenzothiazines 2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-1-one (IDPH-791), C(9)H(7)N(3)OS, (I), a potential muscle relaxant, its benzoyl derivative, 2-(2-oxo-2-phenylethyl)-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-1-one, C(20)H(17)N(3)O(4)S, (II), and the ß-keto ester derivative, ethyl 3-oxo-2-(1-oxo-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]thiazin-2-yl)-3-phenylpropanoate, C(17)H(13)N(3)O(2)S, (III), are the first examples of benzothiazine-fused triazoles in the crystallographic literature. The heterocyclic thiazine rings in all three structures adopt a distorted half-chair conformation. Compound (III) exists in the trans-ß-diketo form. Other than N-H···O hydrogen bonds in (I) forming dimers, no formal intermolecular hydrogen bonds are involved in the crystal packing of any of the three structures, which is dominated by C-H···O/N and π-π stacking interactions.

Tizanidine and tizanidine hydrochloride: on the correct tautomeric form of tizanidine.

A crystallization series of tizanidine hydrochloride, used as a muscle relaxant for spasticity acting centrally as an α(2)-adrenergic agonist, yielded single crystals of the free base and the hydrochloride salt. The crystal structures of tizanidine [systematic name: 5-chloro-N-(imidazolidin-2-ylidene)-2,1,3-benzothiadiazol-4-amine], C(9)H(8)ClN(5)S, (I), and tizanidine hydrochloride {systematic name: 2-[(5-chloro-2,1,3-benzothiadiazol-4-yl)amino]imidazolidinium chloride}, C(9)H(9)ClN(5)S(+)·Cl(-), (II), have been determined. Tizanidine crystallizes with two almost identical molecules in the asymmetric unit (r.m.s. deviation = 0.179 Å for all non-H atoms). The molecules are connected by N-H···N hydrogen bonds forming chains running along [2 ̅11]. The present structure determination corrects the structure determination of tizanidine by John et al. [Acta Cryst. (2011), E67, o838-o839], which shows an incorrect tautomeric form. Tizanidine does not crystallize as the usually drawn 2-amino-imidazoline tautomer, but as the 2-imino-imidazolidine tautomer. This tautomer is present in solution as well, as shown by (1)H NMR analysis. In tizanidine hydrochloride, cations and anions are connected by N-H···Cl hydrogen bonds to form layers parallel to (100).

Enantioselective carbonyl reduction of eperisone in human liver microsomes.

Eperisone, 4-ethyl-2-methyl-3-piperidinopropiophenone, is a centrally acting muscle relaxant widely used to relieve muscle stiffness and back pain. In this study, enantioselectivity for carbonyl reduction of eperisone was investigated in human liver microsomes, and the enzymes involved in the carbonyl reduction were characterised. Carbonyl reduction of eperisone predominantly occurred in microsomal fractions and 11ß-hydroxysteroid dehydrogenase type 1(11ß-HSD 1) played a major role in this reaction as judged by selective inhibition of the activity by BVT-14225 and KR-66344. The kinetic study with (+)-S- and (-)-R-eperisone showed that the formation of the carbonyl reduced metabolite (M5) from the (-)-R-isomer was more efficient than that from the (-)-S-isomer. As eperisone is a racemic compound with one chiral centre, the carbonyl reduced metabolite of eperisone (M5) may have four possible diastereoisomeric structures. Chiral separation of incubation mixtures of racemic eperisone with human liver microsome revealed that (1S, 2S)-M5 and (1R, 2R)-M5 were generated specifically from (+)-S- and (-)-R-eperisone, respectively. Selective formation of anti-diastereomers was further confirmed by incubation of individual enantiomer with microsomes. Carbonyl reduction of eperisone by microsomal 11ß-HSD 1 may significantly contribute to the metabolic disposition of eperisone in human and (-)-R-isomer is preferentially reduced by this enzyme.

Comparison of the therapeutic effectiveness of a dantrolene sodium solution and a novel nanocrystalline suspension of dantrolene sodium in malignant hyperthermia normal and susceptible pigs.

BACKGROUND AND OBJECTIVE: Stopping trigger agents and prompt administration of dantrolene are the cornerstones of treatment of malignant hyperthermia. However, significant time is lost in treatment of the condition because of the cumbersome preparation and administration of the commercially available dantrolene sodium for injection. A potential improvement has become available in the form of a novel nanocrystalline dantrolene sodium suspension (DSS), which is 150 times more concentrated (50 mg ml(-1)) than the standard dantrolene sodium solution (0.33 mg ml(-1)). The aims of this study were to measure the effects of DSS on clinical and laboratory variables in malignant hyperthermia normal pigs and to compare the therapeutic management and clinical effectiveness of DSS with standard dantrolene sodium in a fulminant malignant hyperthermia crisis in susceptible pigs. The pig model is a well accepted method of studying the malignant hyperthermia crisis and is an ideal way to evaluate the variables of interest in this study. METHODS: Seven malignant hyperthermia normal and 10 malignant hyperthermia susceptible pigs were studied. Malignant hyperthermia susceptible pigs (body weight approximately 24 kg) were allocated to a dantrolene sodium group or a DSS group. After induction of anaesthesia, a 22-gauge catheter was placed in an ear vein and trigger-free anaesthesia was performed. After achieving stable conditions, administration of halothane was started with 0.1% and then 0.15%. Halothane was discontinued after the administration of 0.2% (malignant hyperthermia normal pigs) or when a fulminant malignant hyperthermia crisis was achieved (malignant hyperthermia susceptible pigs). After halothane was discontinued, FIO2 was set to 1.0, respiratory minute volume was doubled and sodium bicarbonate 2 mmol kg(-1) was administered. The time required to prepare and administer each formulation was measured. To simulate the administration of the substances under typical clinical conditions for a child weighing approximately 24 kg, dantrolene sodium (5 mg kg(-1)) or DSS (5 mg kg(-1)) was prepared and injected via the intravenous 22-gauge cannula. Bolus administrations of dantrolene sodium or DSS were repeated after 24 min. RESULTS: Arterial pH, arterial pCO2, mean arterial pressure and arterial lactate concentration remained stable during the experiment with DSS in malignant hyperthermia normal pigs. A significant decrease in cardiac index and increases in systemic vascular resistance and serum potassium concentration occurred after administration of DSS. In all malignant hyperthermia susceptible animals, the inhaled administration of halothane 0.15% led to a fulminant malignant hyperthermia crisis. The therapeutic regimens with administration of dantrolene sodium or DSS were successful in treating the malignant hyperthermia crisis in all animals. The course of the malignant hyperthermia crisis and the therapeutic effects of dantrolene sodium or DSS were comparable in the two groups. The time needed to prepare DSS for administration was significantly shorter (51 ± 9 s) compared to dantrolene sodium (860 ± 202 s). The time taken to inject DSS (4 ± 2 s) was significantly shorter than for dantrolene sodium (472 ± 51 s). CONCLUSION: The therapeutic action of DSS in a malignant hyperthermia crisis in pigs was effective and comparable to that of standard dantrolene sodium. However, preparation and administration of DSS were significantly faster, which may offer a clinically significant advantage in the treatment of a fulminant malignant hyperthermia crisis and may result in a reduction in stress for the anaesthesia team.

Formulation and Evaluation of Baclofen-Meloxicam Orally Disintegrating Tablets (ODTs) Using Co-Processed Excipients and Improvement of ODTs Performance Using Six Sigma Method.

PURPOSE: This study aimed to formulate an orally disintegrating tablet (ODT) containing both baclofen and meloxicam together for treating osteoarthritis. METHODS: Direct compression method was used to prepare ODTs using three types of co-processed excipients (Prosolv ODT G2®, F-melt®, and Pharmaburst®500). ODTs were evaluated according to weight variation, thickness, friability, hardness, drug content, wetting time, in-vitro disintegration time, in-vitro dissolution test, and palatability. To enhance the in-vitro dissolution of meloxicam and palatability of ODT, a six sigma methodology was used, and an improvement phase was established where ODTs were prepared using lyophilization and levigation techniques. Finally, a pharmacokinetic study of the improved ODT was accomplished in comparison to the conventional oral tablet. RESULTS: Pharmaburst-based formula (F4) showed the shortest wetting time and, consequently, the shortest disintegration time and the highest percentage of drug dissolved within 3 min compared to the other formulae. All the improved ODTs had a bitterness taste score vary from (0) palatable and (+1) tasteless. The current sigma level was 3.628 σ and 3.33 σ for palatability and solubility of ODT, respectively, which indicated the process was successfully improved compared with the previous sigma level of 2.342 σ of both processes. Pharmacokinetic study of the improved ODTs showed a significant decrease of Tmax to 120 and 30 min instead of 180 and 120 min for meloxicam and baclofen, respectively. CONCLUSION: ODTs were successfully improved using the six sigma methodology, the pharmacokinetic parameters of both drugs were enhanced due to rapid absorption through the oral mucosa.

Occupational allergic contact dermatitis from tetrazepam in nurses.

BACKGROUND: Tetrazepam is a muscle relaxant belonging to the benzodiazepine group. Drug eruptions following ingestion of tetrazepam tablets are well known. OBJECTIVE: To draw the attention to occupational airborne dermatitis and/or hand dermatitis in nurses resulting from crushing of tablets for elderly or disabled people. METHODS: Since 2003, 16 nurses with facial (eyelid) and/or hand dermatitis, suspected to be of occupational origin, were patch tested with the medication they handled during work. RESULTS: Ten nurses presented with a positive patch test reaction to tablets containing tetrazepam, 14 controls remaining negative. Some of them also reacted to other drugs. CONCLUSION: Occupational airborne and/or hand contact dermatitis from tetrazepam might be much more common than suspected by dermatologists, particularly in view of the short period in which all cases have been observed.

Differential Pulse Anodic Voltammetric Determination of Chlorzoxazone in Pharmaceutical Formulation using Carbon Paste Electrode.

The electrochemical behavior of chlorzoxazone at the carbon paste electrode was investigated in 0.04 mol/L Britton-Robinson buffer pH 6.50 using cyclic and differential pulse voltammetric techniques. Cyclic voltammetric studies indicated that the oxidation of the drug was irreversible and controlled mainly by diffusion. Experimental and instrumental parameters were optimized (50 mV/s scan rate, 50 mV pulse amplitude, and 0.04 mol/L Britton-Robinson (BR) buffer pH 6.50 as a supporting electrolyte) and a sensitive differential pulse anodic voltammetric method has been developed for the determination of the drug over the concentration range 0.17-1.68 µg/mL chlorzoxazone, with detection and quantitation limits of 0.05 and 0.16 µg/mL, respectively. The proposed voltammetric method was successfully applied to the determination of the drug in its pharmaceutical formulation (Myoflex tablets), and in spiked human urine samples.

Design, characterization and in vivo evaluation of modified release baclofen floating coated beads.

Baclofen is a centrally acting skeletal muscle relaxant approved by the US Food and Drug Administration (FDA) for the treatment of muscle spasticity, but the immediate release mode of administration and rapid absorption has been associated with adverse effects. The main objective of this study was to prepare modified release floating beads of baclofen in order to decrease the unwanted side effects. The beads were prepared using alginate and coated with Eudragit RS100, Eudragit L100 and cetyl alcohol. They were evaluated for their encapsulation efficiency, buoyance characteristics, morphology, and in vitro release. They have also been tested in vivo for their oral bioavailability and potential side effects. The prepared beads showed floating properties up to 12 h with different lag times ranging from 45.67 to 72.33 sec. Morphological evaluation using scanning electron microscopy (SEM) revealed that the coated beads show smooth with no pores or cracks surfaces. Real-time morphology of the beads during in vitro release testing was studied by the SEM. Optimized formulation of baclofen coated beads exhibited favorable mechanical properties, in addition, it provided extended baclofen release for up to 6 h. In addition, in vivo studies showed that the coated beads effectively decreased the hypotensive side effect associated with rapid plasma peaking from Baclofen® immediate-release tablets. In addition, there were significant differences between the values of Cmax, Tmax, and AUC0-24 of optimized modified release baclofen floating formulations when compared to Baclofen® immediate-release tablets.