Physicochemical Evaluation of Compounded Oral Preparations for Respiratory Illnesses, also known as Mezclitas.

OBJECTIVE: Compounded oral solutions for respiratory illnesses such as the common cold and cough are commonly prepared and dispensed by licensed pharmacists in the United States and Puerto Rico (PR). Standard protocols for their preparation and quality assessment and for patient counseling are available for most of the prescribed compounded solutions. However, in PR there is a common prescription approach colloquially referred to as "mezclitas": mixtures of antitussives, expectorants, decongestants, and other active ingredients available in commercial solutions for which there are no science-driven compounding guidelines for local pharmacists. METHODS: This study evaluated the physicochemical stability of a commonly dispensed compounded preparation (containing guaifenesin, dextromethorphan, and dexamethasone) that is used for the treatment of respiratory illnesses in PR. The stability indicators tested included clarity, odor, pH, and viscosity. Changes in stability indicators were evaluated for different storage conditions (ambient temperature and refrigerated) over a period of 6 months. RESULTS: The samples exhibited small changes in color, odor, and viscosity. Although the observed changes were small, they may be indicative of chemical and/or physical transformations that occurred over time. A survey of local pharmacists also evidenced the absence of standardized protocols for the preparation and dispensation of the mezclitas in PR. CONCLUSION: In spite of the absence of protocols for compounding oral solutions for respiratory illnesses, our study suggests that the stability of such solutions is not heavily compromised. However further chemical and physical testing is needed and the findings of such testing used to develop standardized protocols for the compounding of oral solutions for respiratory illnesses.

Synthesis of a novel magnetic starch-alginic acid-based biomaterial for drug delivery.

The magnetic composite hydrogel was fabricated by the graft copolymerization of itaconic acid (IA) onto starch and Alginic acid in the presence graphene sheets (Gr) and Fe3O4 nanoparticles (Fe3O4@Gr-IA/St-Alg) for Guaifenesin (GFN) delivery and wound healing. The Fe3O4@Gr-IA/St-Alg biomaterial is a hydrogel network endowed the material with magnetic property. In addition, GFN not only achieved effectively bound to the magnetic hydrogel, but also released in a controlled manner. The using external magnetic field has significantly positive influence on the drug release rate. To close, these hydrogel drug carriers offer a favorable platform for magnetically targeted drug delivery as well as a dress for wound healing.

Oral guaifenesin for treatment of filamentary keratitis: A pilot study.

PURPOSE: Pilot study to evaluate the safety and efficacy of oral guaifenesin in reducing the signs and symptoms of filamentary keratitis. METHODS: Prospective, uncontrolled open-label pilot study. Twelve patients with non-Sjögren dry eye disease (DED) and secondary filamentary keratitis received treatment with oral guaifenesin 600 mg twice a day (total dose of 1.2 g/day) for 4 weeks. Adverse events, change in the number of corneal filaments, corneal fluorescein staining (CFS; NEI grading system), and symptoms (Ocular Surface Disease Index) were assessed. RESULTS: Before starting oral guaifenesin, all patients were on topical medical therapy for their condition. At baseline, the mean number of filaments was 5.8 ±â€¯2.9, CFS score 7.3 ±â€¯3.2, and OSDI score 55.6 ±â€¯25. After 4 weeks of treatment, the number of filaments was 2.1 ±â€¯2.2 (p = 0.04 vs. baseline), CFS score 6.5 ±â€¯3.1 (p = 0.5), and OSDI score 46.1 ±â€¯30.9 (p = 0.2). One patient discontinued the medication due to gastrointestinal side effects. CONCLUSIONS: Oral guaifenesin was safe and generally well tolerated, and demonstrated modest efficacy in reducing the severity of filamentary keratitis. These results should be considered preliminary; however, placebo-controlled investigations would be justified to evaluate the therapeutic efficacy of oral guaifenesin as a mucolytic in treatment of filamentary keratitis.

COMPARISON OF ISOFLURANE GAS VERSUS A GUAIFENESIN, KETAMINE, AND MEDETOMIDINE CONSTANT-RATE INFUSION FOR MAINTENANCE ANESTHESIA IN AMERICAN BLACK BEARS (URSUS AMERICANUS).

Published anesthetic protocols for captive and free-ranging bears are limited to injectable inductions with maintenance via inhalants or additional injectable boluses. Though common in other species, intravenous (IV) continuous-rate infusions (CRI) using guaifenesin combinations have not been evaluated in ursids. This study evaluated the use of a CRI compared to an inhalant for maintenance anesthesia. Seven healthy American black bears (Ursus americanus) were anesthetized in a crossover design with two different anesthetic maintenance protocols. Bears were immobilized with ketamine (2.02 ± 0.14 mg/kg) and medetomidine (0.04 ± 0.003 mg/kg) for both protocols. The anesthetic maintenance control protocol consisted of isoflurane gas (ISO) started at 2% delivered by endotracheal tube; the experimental protocol consisted of guaifenesin, medetomidine, ketamine (GMK) IV CRI started at 50 mg/kg/hr guaifenesin, 0.01 mg/kg/hr medetomidine, and 1 mg/kg/hr ketamine. Induction and recovery parameters including time to first effect, recumbency, and hands on; duration of maintenance protocol; and time from reversals administered to head up, standing on all four feet, no ataxia, and to fully recovered were recorded and compared between protocols. Heart rate, respiratory rate, rectal temperature, blood pressure, end tidal carbon dioxide, and hemoglobin oxygen saturation were recorded at 5-min intervals and compared between protocols. Venous blood gases were obtained at the start, middle, and end of the maintenance anesthesia and compared between protocols. All bears exhibited hypertension with mild respiratory acidosis throughout procedures. Measured physiologic parameters did not differ significantly between the isoflurane and the GMK CRI maintenance protocols, with the exception of higher endpoint (ISO) pCO2 measurements. No adverse events were recorded with either protocol, and adequate depth of anesthesia was maintained with both protocols. GMK CRI provides a safe, effective, and more portable alternative to inhalant anesthetics for maintenance anesthesia in bears in captivity or in the field.

Total intravenous anaesthesia with ketamine, medetomidine and guaifenesin compared with ketamine, medetomidine and midazolam in young horses anaesthetised for computerised tomography.

BACKGROUND: There is no information directly comparing midazolam with guaifenesin when used in combination with an alpha-2 agonist and ketamine to maintain anaesthesia via i.v. infusion in horses. OBJECTIVES: To compare ketamine-medetomidine-guaifenesin with ketamine-medetomidine-midazolam for total intravenous anaesthesia (TIVA) in young horses anaesthetised for computerised tomography. STUDY DESIGN: Prospective, randomised, blinded, crossover trial. METHODS: Fourteen weanlings received medetomidine 7 µg/kg bwt i.v. and anaesthesia was induced with ketamine 2.2 mg/kg bwt i.v. On two separate occasions horses each received infusions of ketamine 3 mg/kg bwt/h, medetomidine 5 µg/kg bwt/h, guaifenesin 100 mg/kg bwt/h (KMG) or ketamine 3 mg/kg bwt/h, medetomidine 5 µg/kg bwt/h, midazolam 0.1 mg/kg bwt/h (KMM) for 50 min. Cardiorespiratory variables and anaesthetic depth were assessed every 5-10 min. Recovery times after the infusions ceased were recorded and recovery quality was assessed using a composite score system (CSS), simple descriptive scale (SDS) and visual analogue scale (VAS). Multivariable models were used to generate mean recovery scores for each treatment and each recovery score system and provide P-values comparing treatment groups. RESULTS: Anaesthesia was uneventful with no difference in additional anaesthetic requirements and little clinically relevant differences in cardiopulmonary variables between groups. All horses recovered without incident with no significant difference in recovery times. Quality of the anaesthetic recovery was significantly better for the KMM group compared with the KMG group using the CSS (P<0.001), SDS (P<0.001) and VAS (P<0.001). MAIN LIMITATIONS: No surgical stimulus was applied and study animals may not represent general horse population. CONCLUSION: Midazolam is a suitable alternative to guaifenesin when co-infused with ketamine and medetomidine for anaesthesia in young horses undergoing noninvasive procedures. Both infusions produce a clinically comparable quality of anaesthesia; however, recovery from anaesthesia is of a better quality following an infusion of ketamine-medetomidine-midazolam.

Pharmaceutical Characterization of MyoNovin, a Novel Skeletal Muscle Regenerator: in silico, in vitro and in vivo Studies.

PURPOSE: MyoNovin is a novel skeletal muscle-regenerating compound developed through synthesis of two nitro groups onto a guaifenesin backbone to deliver nitric oxide to skeletal muscle with a potential to treat muscle atrophy. The purpose of this study was to utilize in silico, in vitro, and in vivo approaches to characterize MyoNovin and examine its safety, biodistribution, and feasibility for drug delivery. METHODS: In silico software packages were used to predict the physicochemical and biopharmaceutical properties of MyoNovin. In vitro cardiotoxicity was assessed using human cardiomyocytes (RL-14) while effects on CYP3A4 metabolic enzyme and antioxidant activity were examined using commercial kits. A novel HPLC assay was developed to measure MyoNovin concentration in serum, and delineate initial pharmacokinetic and acute toxicity after intravenous administration (20 mg/kg) to male Sprague-Dawley rats. RESULTS: MyoNovin showed relatively high lipophilicity with a LogP value of 3.49, a 20-fold higher skin permeability (19.89 cm/s*107) compared to guaifenesin (0.66 cm/s*107), and ~10-fold higher effective jejunal permeability (2.24 cm/s*104) compared to guaifenesin (0.26 cm/s*104). In vitro, MyoNovinwas not cytotoxic to cardiomyocytes at concentrations below 8 µM and did not inhibit CYP3A4 or show antioxidant activity. In vivo, MyoNovin had a short half-life (t1/2) of 0.16 h, and a volume of distribution Vss of 0.62 L/kg. Biomarkers of MyoNovincardiac and renal toxicity did not differ significantly from baseline control levels. CONCLUSIONS: The predicted high lipophilicity and skin permeability of MyoNovin render it a potential candidate for transdermal administration while its favourable intestinal permeation suggests it may be suitable for oral administration. Pharmacokinetics following IV administration of MyoNovin were delineated for the first time in a rat model. Preliminary single 20 mg/kg dose assessment of MyoNovin suggest no influenceon cardiac troponin or ß-N-Acetylglucosaminidase. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Evaluation of total intravenous anesthesia with propofol-guaifenesin-medetomidine and alfaxalone-guaifenesin-medetomidine in Thoroughbred horses undergoing castration.

Anesthetic and cardiorespiratory effects of total intravenous anesthesia (TIVA) technique using propofol-guaifenesin-medetomidine (PGM) and alfaxalone-guaifenesin-medetomidine (AGM) were preliminarily evaluated in Thoroughbred horses undergoing castration. Twelve male Thoroughbred horses were assigned randomly into two groups. After premedication with intravenous (IV) administrations of medetomidine (5.0 µg/kg) and butorphanol (0.02 mg/kg), anesthesia was induced with guaifenesin (10 mg/kg IV), followed by either propofol (2.0 mg/kg IV) (group PGM: n=6) or alfaxalone (1.0 mg/kg IV) (group AGM: n=6). Surgical anesthesia was maintained for 60 min at a constant infusion of either propofol (3.0 mg/kg/hr) (group PGM) or alfaxalone (1.5 mg/kg/hr) (group AGM), in combination with guaifenesin (80 mg/kg/hr) and medetomidine (3.0 µg/kg/hr). Responses to surgical stimuli, cardiorespiratory values, and induction and recovery characteristics were recorded throughout anesthesia. During anesthesia induction, one horse paddled in group PGM. All horses from group AGM were maintained at adequate anesthetic depth for castration. In group PGM, 3 horses showed increased cremaster muscle tension and one showed slight movement requiring additional IV propofol to maintain surgical anesthesia. No horse exhibited apnea, although arterial oxygen tension decreased in group AGM to less than 60 mmHg. Recovery quality was good to excellent in both groups. In conclusion, TIVA using PGM and AGM infusion was available for 60 min anesthesia in Thoroughbred horses. TIVA techniques using PGM and AGM infusion provided clinically acceptable general anesthesia with mild cardiorespiratory depression. However, inspired air should be supplemented with oxygen to prevent hypoxemia during anesthesia.

Guaiphenesin-ketamine-xylazine infusion to maintain anesthesia in mules undergoing field castration.

BACKGROUND: In order to determine whether a combination of guaiphenesin, ketamine and xylazine can induce safe and satisfactory anaesthesia in mules undergoing field castration, eight healthy adult intact male mules were employed. They were premedicated with intravenous (IV) xylazine (1.3 mg/kg); an additional dose of xylazine (0.3 mg/kg IV) was administered in case of inadequate depth of sedation. Anaesthesia was induced with IV thiopental (6 mg/kg). The quality of sedation and induction was recorded. Anaesthesia was maintained with an infusion of guaiphenesin (50 mg/mL), ketamine (2 mg/mL) and xylazine (1 mg/mL) (GKX). The spermatic cord of each testis was infiltrated with 5 mL of 2% lidocaine. During anaesthesia heart rate (HR), respiratory rate (RR), rectal temperature (RT) and haemoglobin oxygen saturation (SpO2) were measured every 5 min. The data were analysed with simple one-way analysis of variance (ANOVA). A P value < 0.05 was considered statistically significant. Time of anesthesia, time of surgery and time of recovery were recorded. RESULTS: Only one mule required an additional dose of xylazine to achieve a satisfactory depth of sedation. Thiopental at the dose of 6 mg/kg IV resulted in smooth induction and lateral recumbency in all animals. GKX provided adequate anaesthesia to perform castration in all mules. Muscle relaxation was deemed adequate and physiological variables remained stable and within references values during the anaesthesia and did not change in response to surgical stimulation. Time (mean ± standard deviation) from the end of the infusion to sternal recumbency and time from sternal recumbency to standing were 27.7 ± 4.6 and 30.1 ± 7.7 min, respectively. CONCLUSIONS: The combination of xylazine, thiopental and GKX provides satisfactory short-term anaesthesia in mules undergoing field castration.

Evaluation of intranasal oxygen supplementation in mules anesthetized with the combination of ketamine, butorphanol, and guaifenesin / Avaliação da suplementação intranasal de oxigênio em muares anestesiados com a associação de cetamina, butorfanol e éter gliceril guaiacólico

Hypoxemia is a major complication of field anesthesia and no studies regarding this occurrence in mules has been done. Thus, the aim of this study was to evaluate intranasal oxygen supplementation (IOS) in mules (Equus caballus x Equus asinus) anesthetized with ketamine/butorphanol/guaifenesin combination. For this, we used six male, adult mules (322±29kg) which underwent premedication (MPA) with 0.2mg/kg of midazolam intramuscularly after 15 minutes, 0.02mg/kg detomidine IV 5 minutes after, induction IV with combination of ketamine (2mg/mL), butorphanol (22.5mg/mL), and guaifenesin (50mg/mL) (K/B/G) until lateral decumbency. Maintenance was done with the same anesthetic combination. The animals were submitted twice to the protocol described above, 20 days apart, forming two groups. CG: MPA, induction (0.92±0.24mL/kg (mean±SD)), and maintenance (2.2±0.2mL/kg/h) without SIO; TG: MPA, induction (0.98±0.17mL/kg), and maintenance (2.3±0.4mL/kg/h) with IOS flow 40mL/kg/h. During anesthesia arterial blood was collected every 20 minutes (T0, T20, T40, and T60) for blood gas analysis. Data analyzed by ANOVA followed by the Bonferroni test. P<0.05 was considered significant. Hypoxemia of the animals in the CG in periods (59±5; 55±5; 53±7; 49±8) with lower averages than the TG (160±4, 115±34, 92±25, 81±19) was observed, demonstrating that IOS increases PaO2 avoiding the occurrence of hypoxemia.(AU)

A hipoxemia é uma das principais complicações da anestesia a campo, e em muares não existem estudos a respeito dessa ocorrência. Assim, objetivou-se avaliar a suplementação intranasal de oxigênio (SIO) em muares (Equus caballus x Equus asinus) anestesiados com cetamina/butorfanol/guaifenesina associados. Para isso, foram utilizados seis muares, macho e adultos (322±29kg), submetidos à medicação pré-anestésica (MPA) com 0,2mg/kg de midazolam por via intramuscular, após 15 minutos, 0,02mg/kg de detomidina por via intravenosa, após cinco minutos, indução com administração intravenosa da associação de cetamina (2mg/mL), butorfanol (22,5 µg/mL) e guaifenesina (50mg/mL) em solução de glicose a 5% (C/B/G) até o animal assumir o decúbito lateral. A manutenção foi realizada com a mesma associação anestésica. Os animais foram submetidos duas vezes ao protocolo descrito anteriormente, com intervalo de 20 dias, formando dois grupos experimentais. GC -MPA, indução (0,92±0,24mL/kg (média±DP)) e manutenção (2,2±0,2mL/kg/h) sem SIO; GT - MPA, indução (0,98±0,17mL/kg) e manutenção (2,3±0,4mL/kg/h) com SIO, fluxo de 40mL/kg/h. Durante a anestesia, foi colhido sangue arterial a cada 20 minutos (T0, T20, T40 e T60) para hemogasometria. Os dados foram analisados pela ANOVA, seguidos pelo teste de Bonferroni. Valores de P<0,05 foram considerados significativos. Foi observada hipoxemia (PaO2<60mmHg) dos animais no GC nos tempos avaliados (T0= 59±5; T20= 55±5; T40= 53±7; T60= 49±8), com médias menores que as do GT, (160±4; 115±34; 92±25; 81±19, respectivamente), o que demonstrou que a suplementação intranasal de oxigênio aumenta a PaO2, evitando a ocorrência de hipoxemia.

Pharmacokinetics of guaifenesin following administration of multiple doses to exercised Thoroughbred horses.

Guaifenesin is an expectorant commonly used in performance horses to aid in the clearance of mucus from the airways. Guaifenesin is also a centrally acting skeletal muscle relaxant and as such is a prohibited drug with withdrawal necessary prior to competition. To the authors' knowledge, there are no reports in the literature describing single or multiple oral administrations of guaifenesin in the horse to determine a regulatory threshold and related withdrawal time. Therefore, the objective of the current study was to describe the pharmacokinetics of guaifenesin following oral administration in order to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 2 g of guaifenesin orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum guaifenesin concentrations were determined and pharmacokinetic parameters calculated. Guaifenesin was rapidly absorbed (Tmax of 15 min) following oral administration. The Cmax was 681.3 ± 323.8 ng/mL and 1080 ± 732.8 following the first and last dose, respectively. The serum elimination half-life was 2.62 ± 1.24 h. Average serum guaifenesin concentrations remained above the LOQ of the assay (0.5 ng/mL) by 48 h postadministration of the final dose in 3 of 9 horses.

Guaifenesin Pharmacokinetics Following Single-Dose Oral Administration in Children Aged 2 to 17 Years.

This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age-based doses of 100-400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo ) and terminal volume of distribution (Vz /F) increased with age. Due to a larger increase in Vz /F than CLo , an increase in terminal exponential half-life was also observed. Allometric scaling indicated no maturation-related changes in CLo and Vz /F.

The Effects of Dextromethorphan on Driving Performance and the Standardized Field Sobriety Test.

Dextromethorphan (DXM) is abused most commonly among adolescents as a recreational drug to generate a dissociative experience. The objective of the study was to assess driving with and without DXM ingestion. The effects of one-time maximum daily doses of DXM 120 mg versus a guaifenesin 400 mg dose were compared among 40 healthy subjects using a crossover design. Subjects' ability to drive was assessed by their performance in a driving simulator (STISIM® Drive driving simulator software) and by conducting a standardized field sobriety test (SFST) administered 1-h postdrug administration. The one-time dose of DXM 120 mg did not demonstrate driving impairment on the STISIM® Drive driving simulator or increase SFST failures compared to guaifenesin 400 mg. Doses greater than the currently recommended maximum daily dose of 120 mg are necessary to perturb driving behavior.

Comparison of cardiorespiratory variables in dorsally recumbent horses anesthetized with guaifenesin-ketamine-xylazine spontaneously breathing 50% or maximal oxygen concentrations.

This study compared cardiorespiratory variables in dorsally recumbent horses anesthetized with guaifenesin-ketamine-xylazine and spontaneously breathing 50% or maximal (> 90%) oxygen (O2) concentrations. Twelve healthy mares were randomly assigned to breathe 50% or maximal O2 concentrations. Horses were sedated with xylazine, induced to recumbency with ketamine-diazepam, and anesthesia was maintained with guaifenesin-ketamine-xylazine to effect. Heart rate, arterial blood pressures, respiratory rate, lithium dilution cardiac output (CO), inspired and expired O2 and carbon dioxide partial pressures, and tidal volume were measured. Arterial and mixed-venous blood samples were collected prior to sedation (baseline), during 30 minutes of anesthesia, 10 minutes after disconnection from O2, and 30 minutes after standing. Shunt fraction, O2 delivery, and alveolar-arterial O2 partial pressures difference [P(A-a)O2] were calculated. Recovery times were recorded. There were no significant differences between groups in cardiorespiratory parameters or in P(A-a)O2 at baseline or 30 minutes after standing. Oxygen partial pressure difference in the 50% group was significantly less than in the maximal O2 group during anesthesia.

Comparaison des variables cardiorespiratoires chez les chevaux en décubitus dorsal anesthésiés à l'aide de la guaifénésine-kétamine-xylazine respirant spontanément des concentrations de 50 % ou des concentrations maximales d'oxygène. Cette étude a comparé les variables cardiorespiratoires chez les chevaux en décubitus dorsal anesthésiés à l'aide de guaifénésine-kétamine-xylazine et respirant spontanément des concentrations de 50 % ou des concentrations maximales (> 90 %) d'oxygène (O2). Douze juments en santé ont été assignées au hasard à la respiration de concentrations 50 % ou de concentrations maximales d' O2. Les chevaux ont été mis sous sédation avec de la xylazine, induits au décubitus à l'aide de kétamine-diazépam et l'anesthésie a été maintenue à l'aide de guaifénésine-kétamine-xylazine jusqu'à l'effet. Le rythme cardiaque, la pression artérielle, la fréquence respiratoire, le débit cardiaque par dilution au lithium, l' O2 à l'inspiration et à l'expiration ainsi que les pressions partielles de gaz carbonique et le volume courant ont été mesurés. Des échantillons sanguins artériels et veineux mixtes ont été prélevés avant la sédation (données de référence), durant 30 minutes d'anesthésie, 10 minutes après le débranchement de l'oxygène et 30 minutes après s'être mis debout. La fraction du shunt, l'alimentation en O2 et la différence des pressions partielles d' O2 alvéolaire-artérielle [P(A-a)O2] ont été calculées. Les temps de réveil ont été consignés. Il n'y avait pas de différences significatives entre les groupes dans les paramètres cardiorespiratoires ou dans P(A-a)O2 aux données de référence ou 30 minutes après s'être mis debout. La différence entre la pression partielle de l' O2 dans le groupe 50 % était significativement inférieure à celle du groupe avec des concentrations maximales d' O2 durant l'anesthésie.(Traduit par Isabelle Vallières).

[Therapeutic modalities for the management of cough associated with acute respiratory viral infection, effective in an otolaryngologist's practice].

The objective of the present study was to evaluate the effectiveness ascoril therapy in comparison with the treatment using the mucoactive agent lasolvan in the adult patients suffering from productive cough associated with acute viral respiratory infection. Patients and methods. The study included 120 patients suffering from productive cough associated with acute viral respiratory infection. They were divided into two groups. The patients comprising group 1 (n=6.) were treated with ascoril, those in group 2 (n=60) were given lasolvan. Results. The effectiveness of the treatment of cough in group 1 was found to be higher compared with that in group 2 (p<0.05); moreover, it was associated with better dynamics of certain indicators of the quality of life, such as the social activity level, vitality, and general health (p<0.05). The safety of the proposed treatment was confirmed by the absence of the adverse events throughout the entire treatment period.

Desktop 3D printing of controlled release pharmaceutical bilayer tablets.

Three dimensional (3D) printing was used as a novel medicine formulation technique for production of viable tablets capable of satisfying regulatory tests and matching the release of standard commercial tablets. Hydroxypropyl methylcellulose (HPMC 2208) (Methocel™ K100M Premium) and poly(acrylic acid) (PAA) (Carbopol(®) 974P NF) were used as a hydrophilic matrix for a sustained release (SR) layer. Hypromellose(®) (HPMC 2910) was used as a binder while microcrystalline cellulose (MCC) (Pharmacel(®) 102) and sodium starch glycolate (SSG) (Primojel(®)) were used as disintegrants for an immediate release (IR) layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug (Mucinex(®)) for this study. There was a favourable comparison of release of the active guaifenesin from the printed hydrophilic matrix compared with the commercially available GBT. The printed formulations were also evaluated for physical and mechanical properties such as weight variation, friability, hardness and thickness as a comparison to the commercial tablet and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets) showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian diffusion drug release through a hydrated HPMC gel layer.

The pharmacokinetics of methocarbamol and guaifenesin after single intravenous and multiple-dose oral administration of methocarbamol in the horse.

A simple LC/MSMS method has been developed and fully validated to determine concentrations and characterize the concentration vs. time course of methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred horses. The plasma concentration-time profiles for MCBL after a single intravenous dose of 15 mg/kg of MCBL were best described by a three-compartment model. Mean extrapolated peak (C0 ) plasma concentrations were 23.2 (± 5.93) µg/mL. Terminal half-life, volume of distribution at steady-state, mean residence time, and systemic clearance were characterized by a median (range) of 2.96 (2.46-4.71) h, 1.05 (0.943-1.21) L/kg, 1.98 (1.45-2.51) h, and 8.99 (6.68-10.8) mL/min/kg, respectively. Oral dose of MCBL was characterized by a median (range) terminal half-life, mean transit time, mean absorption time, and apparent oral clearance of 2.89 (2.21-4.88) h, 2.67 (1.80-2.87) h, 0.410 (0.350-0.770) h, and 16.5 (13.0-20) mL/min/kg. Bioavailability of orally administered MCBL was characterized by a median (range) of 54.4 (43.2-72.8)%. Guaifenesin plasma concentrations were below the limit of detection in all samples collected after the single intravenous dose of MCBL whereas they were detected for up to 24 h after the last dose of the multiple-dose oral regimen. This difference may be attributed to first-pass metabolism of MCBL to GGE after oral administration and may provide a means of differentiating the two routes of administration.

[Results of international multicentre non-interventional clinical study of the effectiveness and safety of ascoril expectorant for the treatment of cough in Kazakhstan and Uzbekistan].

This paper reports results of international multicentre non-interventional clinical study of the effectiveness and safety of ascoril expectorant for the treatment of cough in Kazakhstan and Uzbekistan. The study included 16312 patients examined in different cities during 2011-2012. It showed that ascoril expectorant (Glenmark) at a standard dose is an effective agent for the treatment of cough in children above 3 years and adults aged up to 78 years with ARVI and acute bronchitis, exacerbation of these conditions or grade I-II chronic obstructire pulmonary disease. Most patients reported good therapeutic effect within 1 day after intake. Ascoril expectorant caused no adverse reactions and was well tolerated by the patients. 91% of the attending physicians describe the drug as highly effective.

Patient-reported outcomes to assess the efficacy of extended-release guaifenesin for the treatment of acute respiratory tract infection symptoms.

BACKGROUND: Guaifenesin is a component of medicines used to improve symptoms associated with upper respiratory tract infections. Patient-reported outcome instruments are valuable for evaluating symptom improvements; however, a validated tool to assess efficacy of mucoactive drugs does not exist. We compared the efficacy of extended-release guaifenesin with placebo for treatment of symptoms of upper respiratory tract infection using subjective efficacy assessments in a pilot study and confirmed precision of assessments in a validation study. METHODS: The pilot study was a randomized, double-blind study where patients were dosed with either 1200 mg extended-release guaifenesin (n = 188) or placebo (n = 190), every 12 hours for 7 days. Efficacy was assessed using subjective measures including the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and the Wisconsin Upper Respiratory Symptom Survey. End-of-study assessments were completed by patients and investigator. The validation study consisted of two phases. In Phase I, subjects completed interviews to gather evidence to support the content validity of the Daily Cough and Phlegm Diary, the Spontaneous Symptom Severity Assessment and Patient's End-of-Treatment Assessment. Phase II examined the psychometric properties of assessments evaluated in Phase I of the validation study using data from the pilot study. RESULTS: Subjective measures of efficacy at Day 4 showed the most prominent difference between treatment groups, in favor of guaifenesin. The 8-symptom related questions (SUM8) in the Daily Cough and Phlegm Diary, analyzed as a composite score appeared to be the strongest candidate endpoint for further evaluation. Results from the interviews in Phase I supported the content of the assessments which were validated during Phase II. Treatments were well tolerated. CONCLUSIONS: Results from the clinical pilot and validation studies showed that the SUM8 diary scores were robust and reliable for use as efficacy endpoints in studies of mucoactive drugs. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT01046136).

Alfaxalone compared with ketamine for induction of anaesthesia in horses following xylazine and guaifenesin.

OBJECTIVE: To compare anaesthesia induced with either alfaxalone or ketamine in horses following premedication with xylazine and guaifenesin. STUDY DESIGN: Randomized blinded cross-over experimental study. ANIMALS: Six adult horses, five Standardbreds and one Thoroughbred; two mares and four geldings. METHODS: Each horse received, on separate occasions, induction of anaesthesia with either ketamine 2.2 mg kg(-1) or alfaxalone 1 mg kg(-1) . Premedication was with xylazine 0.5 mg kg(-1) and guaifenesin 35 mg kg(-1) . Incidence of tremors/shaking after induction, recovery and ataxia on recovery were scored. Time to recovery was recorded. Partial pressure of arterial blood oxygen (PaO(2) ) and carbon dioxide (PaO(2) ), arterial blood pressures, heart rate (HR) and respiratory rates were recorded before premedication and at intervals during anaesthesia. Data were analyzed using Wilcoxon matched pairs signed rank test and are expressed as median (range). RESULTS: There was no difference in the quality of recovery or in ataxia scores. Horses receiving alfaxalone exhibited a higher incidence of tremors/shaking on induction compared with those receiving ketamine (five and one of six horses respectively). Horses recovered to standing similarly [28 (24-47) minutes for alfaxalone; 22 (18-35) for ketamine] but took longer to recover adequately to return to the paddock after alfaxalone [44 (38-67) minutes] compared with ketamine [35 (30-47)]. There was no statistical difference between treatments in effect on HR, PaO(2) or PaCO(2) although for both regimens, PaO(2) decreased with respect to before premedication values. There was no difference between treatments in effect on blood pressure. CONCLUSIONS AND CLINICAL RELEVANCE: Both alfaxalone and ketamine were effective at inducing anaesthesia, although at induction there were more muscle tremors after alfaxalone. As there were no differences between treatments in relation to cardiopulmonary responses or quality of recovery, and only minor differences in recovery times, both agents appear suitable for this purpose following the premedication regimen used in this study.

Evaluation of the clinical efficacy of two partial intravenous anesthetic protocols, compared with isoflurane alone, to maintain general anesthesia in horses.

OBJECTIVE: To compare the ability of 2 partial IV anesthesia (PIVA) techniques to maintain anesthesia, compared with isoflurane alone, in horses. ANIMALS: 45 horses. PROCEDURES: Client-owned horses requiring general anesthesia for a variety of procedures of at least 1 hour's duration were randomly allocated to 3 groups (n = 15/group) that differed for the maintenance protocol. Anesthesia was maintained with isoflurane with a starting end-tidal isoflurane concentration of 1.3% (isoflurane group) or a concentration of 1% supplemented with an adjustable continuous infusion of guaifenesin-ketamine (IGK group) or romifidine-ketamine (IRK group). A predefined scoring system was used to assess anesthetic depth and to adjust anesthetic delivery. The need for rescue anesthetics and recovery quality were compared. RESULTS: A mean ± SD end-tidal isoflurane concentration of 1.36 ± 0.16% was necessary to maintain a surgical plane of anesthesia in the isoflurane group. Mean infusion rates of 5.0 ± 1.3 µL/kg/min and 5.1 ± 0.8 µL/kg/min were necessary to maintain a surgical plane of anesthesia in the IRK and IGK groups, respectively. A lower need for ketamine as a rescue anesthetic was observed in the IGK group, compared with the isoflurane group. Higher blood pressure and lower heart rates were found at selected time points for the IRK group, compared with the IGK and isoflurane groups. CONCLUSIONS AND CLINICAL RELEVANCE: Both PIVA protocols were satisfactory to maintain smooth and stable surgical anesthesia in horses. The present study supports previous findings in which PIVA has isoflurane-sparing effects. Furthermore, PIVA did not impair recovery quality.