Clinical and radiological outcome of combined femoral and Chiari osteotomies for subluxed or dislocated hips secondary to neuromuscular conditions: a minimum of 10-year follow-up.

We evaluated the medium-term results of combined Chiari pelvic and femoral osteotomies performed at the Manchester Children's Hospitals between the years 1985 and 1994. The indications for these osteotomies were either hip dislocation or subluxation in children with neuromuscular disease. We clinically and radiologically evaluated 20 hips in 18 patients treated for hip subluxation and dislocation with Chiari osteotomy. The average post-operative clinical follow-up period was 11.32 years (range 10.1-12.9). The mean age at the time of surgery was 7.3 years (range 3.1-13.2 years). Clinically, 9 hips had a 'Good' outcome, 10 were "Fair" and 1 was "Poor" according to Osterkamp criteria. At last follow-up, radiologically the mean Sharp's angle improved from 51° to 44° (p = 0.09), the mean Centre-Edge angle improved from -16° to 18° (p = 0.067), the mean Migration Index improved from 59 to 29 % (p = 0.011), the mean femoral neck-shaft angle from 160° to 117° (p < 0.0001) and the Severin criteria improved from an average grade of 4.5-2.9 (p < 0.0001). Our results compared to previous studies confirm that combined femoral and Chiari osteotomies provide a favourable outcome both clinically and radiologically at least 10 years following surgery. Accepting that the numbers are small, we report no statistical difference in the mean age at the time of operation when comparing the children with an eventual 'good' outcome and those with an eventual 'fair' or 'poor' outcome.

Transdermal drug delivery of labetalol hydrochloride: Feasibility and effect of penetration enhancers.

OBJECTIVES: The objective of this study is to investigate the feasibility of transdermal drug delivery of Labetalol Hydrochloride (LHCl) and to study the effect of different penetration enhancers on the skin permeability of LHCl. METHODS: The permeability experiments were conducted using a horizontal glass diffusion cell with a diffusional area of 2.37 cm-(2) on albino rat skin. The effect of various penetration enhancers namely turpentine oil, dimethyl formamide (DMF), menthol, dimethyl sulfoxide, pine oil, and 2-pyrollidone, and the effect of the concentration of drug and enhancer in the donor phase on the skin permeability of LHCl was studied. RESULTS: The apparent partition coefficient of the drug was found to be 6.95, suggesting it to be a lipophilic drug. The preliminary skin permeation studies revealed that the permeation of LHCL through albino rat skin was moderate (K(p) = 6.490 × 10(-2) cm hr(-1)) from isotonic phosphate buffer of pH 7.4. An appreciable increase in the LHCl permeability coefficient was observed on using a co-solvent (ethanol 95%) with the penetration enhancers in the donor phase. DMSO (10% v/v) was found to be the most effective enhancer for Labetalol hydrochloride (Enhancement Factor = 1.165). An increase in the concentration of drug and enhancer in the donor cell accentuated the permeability coefficient of LHCl. CONCLUSIONS: It was concluded that LHCl could be delivered via the dermal route with the use of 10% DMSO as the penetration enhancer.

Transdermal drug delivery of labetolol hydrochloride: system development, in vitro; ex vivo and in vivo characterization.

OBJECTIVE: The aim of the present work was to develop and evaluate matrix type transdermal drug delivery systems (TDDS) of labetolol hydrochloride (L-HCL) effective for 48 hours. EXPERIMENTAL: The TDDS were prepared by solvent evaporation technique. Six formulations (carrying Eudragit RL100:Eudragit RS 100 in 7.5:4.5, 5.0:5.0, 3.5:8.5 in formulations X-1, X-2, X-3 and Eudragit RL100:PVP K-30 in 9.0:2.0, 5.0:5.0, 4.0:7.0 in formulations Y-1, Y-2, Y-3, respectively) were prepared. All formulations carried 36% w/w of L-HCL, 10-12% w/w of enhancer dimethyl sulfoxide and 2.5-7.5% w/w of plasticizer PEG 400 in methanol-acetone solvent system. The TDDS were evaluated by in vitro drug release, ex vivo skin permeation, stability and in vivo pharmacodynamic studies. RESULTS: The maximum drug release for X-series was 90.26% in 48 hours (X-1) and for Y-series, it was 83.24% (Y-1). Again formulations X-1 (Kp = 0.221x10(-2) cm hr(-1)) and Y-1 (Kp = 0.210x10(-2) cm hr(-1)) exhibited the best skin permeation potential in the respective series. This might be due to higher permeability characteristics of Eudragit RL100. A shelf life of 2.38 years was predicted for the TDDS. Mean systolic BP of the experimental hypertensive rats was significantly reduced (p<0.01) on TDDS treatment. CONCLUSION: The TDDS holds promise for clinical trials.