Feasibility of pair-housing of rats after cranial implant surgery.

Rat models employing cranial implants are increasingly employed to facilitate neural stimulation and recording in freely moving animals. Due to possible damage to wound, implant or attached devices, rats with cranial implants are traditionally housed singly, and little information is available on group- or pair-housing. Here we describe a protocol for pair-housing rats following cranial implant surgery and describe our experience with pair-housing during post-surgical recovery and up to 16 weeks following surgery.Thirty-six adult Wistar rats of both sexes were implanted with deep brain stimulation electrodes. Ten rats were equipped with an additional wireless headstage. Rats were housed in stable pairs before surgery and re-introduced 0-18 h post-surgery. Rat grimace scores did not indicate pain after conclusion of the analgesia protocol, physiological parameters were in the normal range three days post-surgery and weight loss did not exceed 10%. Rats with a cement cap only were pair-housed continuously without damage to the headcap. Rats carrying an additional fragile headstage had to be separated during lights-off periods to prevent headstage damage but could be pair-housed during lights-on periods.Pair-housing is a feasible and effective method to facilitate the rats' need for social companionship following cranial implant surgery.

Development and Validation of a Discriminative Dissolution Medium for a Poorly Soluble Nutraceutical Tetrahydrocurcumin

Objectives: The present study aimed to develop and validate a discriminative dissolution method for tetrahydrocurcumin (THC), a Biopharmaceutical Classification System class II drug, by a simple ultraviolet (UV) spectrophotometric analysis. The final dissolution medium composition was selected based on the solubility and stability criteria of the drug. Materials and Methods: As a prerequisite for this, the solubility of the drug was assessed in media of different pH (1.2-7.4), and surfactant concentrations of 0.5-1.5% (w/v) sodium lauryl sulfate (SLS) in water, and pH 7.4 phosphate buffer. The dissolved drug concentration in each medium was quantified by UV analysis at 280 nm wavelength. Results: The drug solubility was found to be high at a pH of 1.2 and 7.4. The media with surfactant enhanced solubility of the drug by approximately 17-fold and exhibited better sink conditions. The discriminative power of the developed dissolution medium (i.e., 1% w/v SLS in pH 7.4) was determined by performing in vitro dissolution studies of the prepared THC tablets and comparing their release profiles using fit factors (f1 and f2). The results of the fit factor comparisons made between the dissolution profiles of THC tablets proved the discriminative ability of the medium. The validation of the developed dissolution method was performed by international guidelines and the method showed specificity, linearity, accuracy, and precision within the acceptable range. Conclusion: The proposed dissolution method was found to be adequate for the routine quality control analysis of THC, as there is no specified dissolution method for the drug in the pharmacopoeia.

Estimation of dispersive properties of encapsulation tissue surrounding deep brain stimulation electrodes in the rat.

The aim of this study was to estimate the electrical properties of the encapsulation tissue surrounding chronically implanted electrodes for deep brain stimulation in the rat. The impedance spectrum of a concentric bipolar microelectrode implanted in the rat brain was measured immediately following surgery and after 8 weeks of implantation. The experimental impedance data were used in combination with a finite element model of the rat brain using a parametric sweep method to estimate the electrical properties of the tissue surrounding the electrode in acute and chronic conditions. In the acute case, the conductivity and relative permittivity of the peri-electrode space were frequency independent with an estimated conductivity of 0.38 S/m and relative permittivity of 123. The electrical properties of the encapsulation tissue in the chronic condition were fitted to a dispersive Cole-Cole model. The estimated conductivity and relative permittivity in the chronic condition at 1 kHz were 0.028 S/m and 2×105, respectively. The estimated tissue properties can be used in combination with computational modeling as a basis for optimization of chronically implanted electrodes to increase the efficacy of long-term neural recording and stimulation.

Production of Irbesartan Nanocrystals by High Shear Homogenisation and Ultra-Probe Sonication for Improved Dissolution Rate.

Irbesartan (IRB) is a BCS class II drug with poorly aqueous solubility and its absorption is dissolution rate limited. In the present study solubility and dissolution rate of IRB were improved by nanonization and using two poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) amphiphiles, namely Pluronic® F127 and Pluronic® F68, as nanosuspension stabilisers. In addition, the role of these surfactants in the solubilization of the drug was assessed. The nanocrystals were produced by two top-down techniques- high shear homogenisation and ultra-probe sonication. The nanocrystals were characterized for particle size, size distribution and zeta potential and compared to the unprocessed drug by FTIR, thermal analysis, scanning electron microscopy, solubility and dissolution rate. IRB nanocrystals showed greater solubility and faster dissolution rate than the original drug, solubility being higher for formulations prepared with F127 than those with F68. Presence of an endothermic peak of drug in the formulation confirmed its crystalline nature, regardless of the use of two energetic methods. SEM of the nanocrystals revealed a small rod-shaped morphology and the substantial decrease of the particles size. Overall results support these nanonization techniques as a simple, cost-effective and scalable approach to improve the aqueous solubility of drugs such as IRB that are classified into Class II of the Biopharmaceutic Classification System (BCS).