Five (5) Beagle dogs and twelve (12) cynomolgus monkeys were used to generate representative data with the model, and their response to the positive control drug (PTZ) (see the Experimental methods section). At onset of treatment, Beagle dogs were 10 months old and cynomolgus monkeys were 2 years old. Prophylactic antibiotics (Baytril, Bayer Health Care, Toronto, ON, Canada; 0.1 mL/kg, 50 mg/mL; Penicillin G procaine, Vetoquinol, Lavaltrie, QC, Canada; 0.4 mL, 300 000 IU/mL) were administered by intramuscular (IM) injection prior to surgery and daily for at least two days. Preemptive analgesia was attained via a transdermal Fentanyl patch

(Sandoz, QC, Canada; 12.5 μg/h) over three days. An antibiotic, Cefazolin (Novopharm, Markham, ON, Canada; 0.4 mL/kg, 80 mg/mL) was applied to the skull surgical site. A local anesthetic (Bupivacaine, INCB018424 concentration Hospira, Montreal, QC, Canada, 0.25%, 0.5 mL; or Lidocaine, Vetoquinol, Lavaltrie, QC, Canada; 20 mg/mL, 0.5 mL) was injected (0.1–0.2 mL) in 6–10 subcutaneous (SC) sites distributed over the skull surgical site to ensure a multimodal analgesia. Animals were placed on a heating pad and inhaled a mixture of oxygen (O2) and isoflurane (AErrane, Baxter Corporation, Mississauga, ON, Canada). Respiratory rate was maintained between 8 and 20 breaths/min with an inspiratory airway pressure between 18 and 25 cm GSK126 nmr H2O using a mechanical ventilator (Hallowell

EMC, Pittsfield, MA, USA). Heart rate, pulse oximetry (SpO2) and body temperature were monitored continuously during anesthesia. A longitudinal incision

was performed lateral but close to the linea alba, and the internal abdominal oblique muscle was separated from the aponeurosis of the transversus abdominis. The telemetry transmitter was placed between the internal abdominal oblique muscle and the aponeurosis of the transversus abdominis muscle. The rectus abdominis was sutured with a simple continuous suture and EEG electrodes were tunneled subcutaneously to a small skin incision in the neck. Electroencephalographic leads (TL11M2-D70-EEE, Data Science International, Phosphoprotein phosphatase St.-Paul, MN, USA) were secured on to the skull bones to monitor three standard bipolar derivations (C3-O1, C4-O2 and Cz-Oz) using the 10–20 electrode system. A linear groove was done in the cranial cortical bone to secure the electrodes with surgical glue (Vetbond, 3M, St-Paul, MN, USA) and acrylic. Electromyographic (EMG) recording was obtained using electrodes sutured to longitudinal muscles in the neck area and recorded continuously with the telemetry transmitter. A period of three weeks was allowed between surgery and the start of experimental procedures. An additional ten (10) cynomolgus monkeys (3.5–6 years old), maintained under the same environmental conditions as described above, were surgically prepared with the same telemetry transmitters (TL11M2-D70-EEE, Data Science International, St.

These delivery systems use skin as either a rate controlling barrier to drug absorption or as a reservoir for drug.2 This technology was successfully utilised for developing various drugs like, nitroglycerine, oestradiol, clonidine, nicotine

and testosterone patches. This route maximises bio-availability, thereby optimising the therapeutic efficacy and minimises the side effects.3 Present work was aimed at developing a matrix drug delivery system using a model anti hypertensive agent, losartan potassium (LP), an angiotensin II receptor (type AT1) antagonist. Rationality of selecting losartan learn more was based on various physicochemical, pharmacokinetic and pharmacodynamic parameters.4 Physicochemical parameters include molecular weight (461.0), pka (4.9) and melting point – 183.5 °C to 184.5 °C Pharmacokinetic and pharmacodynamic parameters include plasma elimination half life 1.5–2.5 h, bioavailability 33%. Usage of polymethylmethacrylate is widely seen as a component in eudragit mixtures.5 Ethyl cellulose, a hydrophobic polymer finds its usage in TD delivery.6 In the present study hydrophobic polymers were selected to prepare patches of losartan potassium which is a hydrophilic drug. Release profile was observed by altering the concentrations of these two polymers. DMSO, sulfoxides

class of enhancers, was used.3, 7, 8 and 9 and PEG-400, as plasticizer were used.10 The prepared patches were tested for various physicochemical Sirolimus supplier parameters and in vitro drug release using dialysis membrane. 11 Losartan was purchased from SL Drugs, Hyderabad. PMMA was purchased from Himedia laboratories, Mumbai. All other chemicals of pharmaceutical grade, are purchased from SD Fine Chemicals, Mumbai. The films were prepared as given in the Table 1 and solvent casting technique was used to prepare the films. A dispersion of polymers was prepared by dissolving PMMA and then EC to form a matrix in chloroform. Then losartan was separately dissolved in chloroform, containing 5% v/v methanol and was added to the polymer dispersion and mixed thoroughly to facilitate distribution of drug in the polymer matrix. To the formed dispersion

required amount of PEG-400 and DMSO were added one after the other and mixed. Resultant dispersion was checked for any air entrapment and was poured in a glass petri plate of known area 70 cm2 and allowed to dry overnight whatever at room temperature by inverting a funnel to ensure uniform evaporation of the solvent. Dried patches were removed from petri plate and stored in a dessicator with aluminium foil wrapping for further evaluation. UV spectrophotometric method based on the measurement of absorbance at 254 nm in phosphate buffer of pH 7.4 was used to estimate the drug content in the prepared transdermal patches. The method obeyed Beer’s law in the concentration range of 5–40 μg/ml and was validated for linearity, accuracy and precision. No interference with excipients was observed.