Influence of different formulation variables on the performance of transdermal drug delivery system containing tizanidine hydrochloride: in vitro and ex vivo evaluations

The present study was aimed at preparation of transdermal patches of tizanidine HCl, evaluation of the effect of polymers on in vitro release pattern of the drug, and the effect of permeation enhancers on the penetration of the drug through the rabbit skin. Various proportions of hydrophilic (HPMC) and hydrophobic (Eudragit L-100) polymers were used with PEG 400 as film-forming agent, and Span 20 or DMSO as permeation enhancer. The formulations were assessed for physicochemical characteristics and in vitro drug release studies using USP paddle over disc method in phosphate buffered saline (pH 7.4) at 32.0±1°C. On the basis of in vitro studies and physicochemical evaluations, S03-A and S04-A were selected at Eudragit : HPMC ratios of 8 : 2 and 7 : 3, respectively, for further ex vivo analysis. The effects of different concentrations of Span 20 and DMSO were evaluated on excised rabbit skin using Franz diffusion cell. Cumulative drug permeation, flux, permeability coefficient, target flux, and enhancement ratio were calculated and compared with the control formulations. Kinetic models and Tukey's multiple comparison test were applied to evaluate the drug release patterns. Formulation SB03-PE containing Eudragit L-100:HPMC (7:3) with Span 20 (15% w/w) produced the highest enhancement in drug permeation, and followed zero order kinetic model with super case-II drug release mechanism.

The clinical outcome of urethroplasty using acellular dermal matrix patch for the treatment of anterior urethral stricture caused by lichen sclerosus / 中国医师进修杂志

Objective To summarize the clinical effect of urethroplasty using acellular dermal matrix patch for the treatment of anterior urethral stricture caused by lichen sclerosus.Methods The clinical data was analyzed retrospectively from 15 patients with anterior urethral stricture caused by lichen sclerosus treated with aeellular dermal matrix patch.Results The patients were followed up for 8-40 months.The urethral silicone stent was removed 4 weeks after operation in 15 cases and all the patients voided well 2 months after operation.The urinary peak flow rates ranged from 17.6 to 41.7 ml/s(mean,28.6ml/s).Urethral stricture occurred in 2 patients 3 months after operation undergoing discontinuous dilatation within 3 to 6 months,the patients voided very well.Conclusion It is feasible,safe and relatively simple to use acellular dermal matrix patch for anterior urethral stricture caused by lichen sclerosus.

Clinical Usefulness of Fentanyl Matrix Patch for the Patients with Chronic Low Back Pain

STUDY DESIGN: Prospective observational study. OBJECTIVES: The aim of this study was to examine the usefulness of a fentanyl matrix patch in the management of chronic low back pain. SUMMARY OF LITERATURE REVIEW: Chronic low back pain is a significant disabling disease with high medical costs and socioeconomical effects. Oral medication is a fundamental tool for conservative treatment. The fentanyl matrix patch is currently regarded as an alternative method for oral medication, however, the usefulness of the fentanyl matrix patch has not been fully evaluated. MATERIALS AND METHODS: From September 2008 to May 2009, a multicenter, open, prospective observational study was conducted. The inclusion criteria included chronic pain patients that did not respond to conservative pain management. The clinical usefulness was evaluated with pain intensity, and the KEQ-5D (Korean version of Euro QoL-5 dimension). RESULTS: Overall, 538 patients were included in this study. The pain intensity decreased about 1.84 +/- 1.91 at the second visit and further decreased by about 2.52 +/- 2.34 at the third visit (p<0.0001). The KEQ-5D score decreased about 0.12 +/- 0.18 at the second visit, and decreased further to 0.18 +/- 0.24 at the third visit (p<0.0001). The number of patients with adverse effects was 121 (22.49%). CONCLUSIONS: The fentanyl matrix patch improves the pain and disability in patients with chronic low back pain. It is a useful alternative method for the management of chronic low back pain.

Buprenorfina transdérmica en el manejo del dolor crónico nociceptivo y neuropático no oncológico en ortopedia / Buprenorfine transdermal matrix patch in the treatment of chronic nociceptive non malignant pain and neurophatic pain in the orthopaedic patology

Objetivo: siendo el año del dolor musculoesquelético, es importante evitar el subtratamiento, dado la prevalencia de dolor crónico, los costos, limitación funcional y disminución de la calidad de vida en el paciente ortopédico, requiriéndose de vías menos invasivas, como la administración transdérmica, a través de sistema matricial de buprenorfina, en base a su liposolubilidad, y biodisponibilidad, sin riesgo de hiperalgesia ni afectación del sistema inmune, considerando su efecto techo en depresión respiratoria, y su empleo en comorbilidad renal y hepática. Material y métodos: estudio longitudinal, prospectivo, aleatorizado, de septiembre de 2008 a febrero de 2010, en el servicio de algología de orthocaz, unidad de ortopedia. N=108 de ambos sexos bajo consentimiento informado. Resultados: prevalencia de dolor en consulta externa de ortopedia r= 60-80 por ciento, x = 70, el crónico nociceptivo mayor de 30 por ciento y neuropático 1, 5 por ciento con predominio en el sexo femenino de 53,8 por ciento y, etiológicamente, el síndrome de columna fallida ocupa 40,7 por ciento, osteoartrosis 44, 4 por ciento, edad X= 66,59 años r= 20-85, dolor neuropático crónico secundario a metástasis en columna lumbar 3,7. La causa más común fue cáncer prostático, síndrome complejo regional 3,7 por ciento, el tamaño del efecto (EZ) fue de 1,2 el NNT= 4, a la 3ra semana se incrementó el dolor incidental e irruptivo, a partir del 10º día disminuyeron los efectos secundarios, como la somnolencia y nausea. Discusión y conclusiones: la osteoartritis, el síndrome de columna fallida, conducto lumbar estrecho mixto, síndrome complejo regional, secuelas de fracturas, prótesis fallidas, secuelas de displasia del desarrollo de la cadera, síndrome doloroso lumbar crónico, son padecimientos musculoesqueléticos en el que se aceptan el manejo de opiodes clase 3 de la OMS, de libración prolongada, como la buprenorfina...

Objetive: being the international year of the pain skeletal muscle, it is important to avoid the sub treatment, dice the prevalence of chronic pain, with the costs, functional limitation and diminution of the quality of life in the orthopedic patient requiring itself of less invasive routes as it is it the transdermal administration through matrix system of buprenorfina, on the basis of his high lip solubility without risk of hiperalgesia nor affectation of inmune system, considering his effect ceiling in respiratory depression, and its use in renal and hepatic comorbidity. Material and methodology: longitudinal, prospective study, randomized, of September of the 2008 to February 2010, in the service of algology of Orthocaz unit of N= orthopedics 108 both sexes, under informed consent. Results: Prevalence of pain in external consultation of orthopedics r= 60-80 per cent, x =70, the chronic greater nociceptive of 30 percent and neurophatic 1,5 percent with predominance in 53,8 percent feminine sex etiology the syndrome of insolvent column occupies 40,7 percent, osteoartrosis 44,4 percent, X= age 66,59 years, r= 20-85, secondary chronic neuropathic pain to metastasis in 3,7 lumbar column the cause most common prostate cancer, regional complex syndrome 3,7 percent the size of effect (EZ) the EU of 1,2 NNT= 4, to third week increase the incidental and irruptive pain, from the 10 day diminished the indirect effect, as drowsiness and feels nauseous. Discussion and and conclusions osteoarthritis, syndrome of insolvent column, lumbar conduit narrow compound, regional complex syndrome, sequels of fractures, prosthesis insolvent, sequels of dysplasia of the developement of the hip, chronic lumbar painful syndrome, are sufferings skeletal muscle in wich the handing of opiods is accepted class III, of the WHO of liberation prolonged as it is it buprenorfina transdermal, wih progressive degree, and to allow tolerability.

Influence of body fat in cancer patients on residual content of used fentanyl matrix patches

<b>Purpose</b>: The objective of this study was to investigate whether body fat rate (BFR) and triceps skinfold thickness (TSF) are associated with estimated fentanyl absorption in patients treated with the fentanyl transdermal matrix patch for moderate to severe cancer pain, by measuring the residual content of fentanyl in used matrix patches. <b>Methods</b>: Adult Japanese inpatients experiencing chronic cancer-related pain and receiving treatment for the first time with a transdermal fentanyl matrix patch (Durotep®MT patch) were included in the present study. During the initial application period, BFR was measured using a body fat scale, and TSF was measured by an experienced nurse with an adipometer. One patch was collected from each patient. The residual fentanyl content in used matrix patch was determined by high-performance liquid chromatography. The transdermal fentanyl delivery efficiency was estimated based on the fentanyl content of the used matrix patches. <b>Results</b>: Fifteen adult patients (5 males and 10 females) were included in this study. Nine patches with a release rate of 12.5μg/h and 6 patches with a release rate of 25μg/h were collected. The application site was the chest or upper arm. BFR and TSF both showed a significant positive correlation with delivery efficiency. <b>Conclusion</b>: In malnourished or low-body fat patients receiving DMP, pain intensity should be more carefully monitored, and fentanyl dose adjustment may be required. Additional parameters, such as nutritional status including body fat change, the degree of dry skin, and plasma fentanyl concentration, also require detailed evaluation. Palliat Care Res 2010; 5(2): 206-212

The effective rotation dose from fentanyl transdermal patch to other opioids

<b>Purpose</b>: A case of effective pain control by opioid rotation from fentanyl patch (oral morphine:fentanyl=100: 1 ratio) was succeeded with less than the theoretically equivalent conversion dose. Therefore, an investigation was undertaken to determine the effective rotation dose from fentanyl patch to other opioids. <b>Methods</b>: Retrospective analysis was carried out on patients with cancer-related pain, who were switched from fentanyl patch to other opioids. <b>Results</b>: Fourteen patients were analyzed and the average effective dose of opioids after the rotation was 76% of the theoretically calculated dose. Effective doses after opioid rotation were less than calculated doses in 11 cases (79%) and more than calculated doses in only 3 cases (21%). Effective doses after opioid rotation were 101% of calculated doses in cases (n=5) with less than 75μg/hr of fentanyl patch, but 63% in cases (n=9) with more than 75μg/hr. <b>Conclusion</b>: Opioid rotation should be considered when administration of more than 75μg/hr of fentanyl patch is needed. It is necessary to reduce the amount of applied dose to approximately 60% of calculated dose for safe opioid rotation. Moreover, it is necessary to remain careful and to provide immediate assistance in case of emergency due to withdrawal syndrome. Palliat Care Res 2009; 5(1): 301-307