Use of 5% lidocaine patch in the management of post-traumatic localized neuropathic pain. Case reports / O uso do emplastro de lidocaína a 5% no manejo de dor neuropática localizada pós-traumática. Relato de casos

ABSTRACT BACKGROUND AND OBJECTIVES: Neuropathic pain is defined as a pain caused by a lesion or condition that affects the somatosensory nervous system. Taking its prevalence into account, in particular post-traumatic localized neuropathic pain, and to discuss ways to manage patients with this condition, considering efficacy and tolerability of proposed treatments, this report presents three clinical cases of patients with post-traumatic localized neuropathic pain treated with 5% lidocaine transdermal patch in both monotherapy and polytherapy. CASE REPORTS: This study reports the cases of three female patients aged between 29 and 81 years with complaints of pain due to trauma, who were managed with 5% lidocaine transdermal patch in prolonged treatment, with a significant improvement in pain. CONCLUSION: According to scientific evidence, the use of 5% lidocaine transdermal patch in post-traumatic localized neuropathic pain as shown efficacy with favorable safety and tolerance. Moreover, it was possible to demonstrate that a 5% lidocaine transdermal patch in a polytherapy format has contributed to improved outcomes with no effect in treatment tolerability.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor neuropática é definida como uma dor provocada por uma lesão ou doença que afeta o sistema nervoso somatossensitivo. Considerando a sua prevalência, em particular dor neuropática localizada pós-traumática, com o intuito de discutir formas de manejar os pacientes portadores dessa condição e avaliando tanto a eficácia quanto a tolerabilidade aos tratamentos propostos, este artigo apresenta três casos clínicos de pacientes portadores dessa condição, tratados com emplastro de lidocaína a 5%, tanto em monoterapia quanto no contexto da terapia multimodal. RELATOS DOS CASOS: Este estudo relata três casos de pacientes do sexo feminino com idades entre 29 e 81 anos e queixas de dor decorrente de trauma, que foram manejadas com emplastro de lidocaína a 5% em tratamento prolongado, com uma significativa melhora do nível de dor. CONCLUSÃO: Em concordância com as evidências da literatura científica, o uso do emplastro de lidocaína a 5% nos casos de dor neuropática localizada pós-traumática relatados mostrou-se eficaz no manejo dessa condição e apresentou perfil de segurança e tolerabilidade favorável. Além disso, foi possível observar também que o emplastro de lidocaína a 5%, quando adicionado em abordagem multimodal, contribuiu para uma melhora no quadro sem prejuízo da tolerabilidade do tratamento.

Parches transdérmicos anticonceptivos: evaluación de tecnología sanitaria / Contraceptive transdermal patches: health technology assessment

INTRODUCCIÓN: La anticoncepción es un derecho, y es obligación del Estado garantizar el acceso a métodos anticonceptivos efectivos, seguros y de calidad. Se realizó una evaluación de tecnología sanitaria sobre los parches anticonceptivos transdérmicos. MÉTODOS: Un equipo multidisciplinario e independiente designado por el Comité Provincial de Biotecnologías de Neuquén buscó información epidemiológica, regulatoria y evidencias científicas sobre eficacia, seguridad y adherencia. Se analizó y sistematizó siguiendo metodología GRADE (Grading of Recommendations Assessment, Development and Evaluation) y CASPe (Critical Appraisal Skills Programme Español). RESULTADOS: El único parche autorizado en Argentina para su comercialización libera 33,9 µg/día de etinilestradiol y 203 µg/día de norelgestromina. Su prospecto en Argentina, EE.UU. y Europa lo asocia al doble de riesgo de enfermedad tromboembólica venosa si se compara con las píldoras anticonceptivas que provee el Estado. Esto coincide con resultados de estudios de cohortes de alta calidad. Los parches proveen similar eficacia anticonceptiva a corto plazo, pero con altas tasas de abandono en el seguimiento. La Organización Mundial de la Salud no los ha incluido en su listado de medicamentos esenciales. Los parches son más costosos que otros métodos disponibles. DISCUSIÓN: Sobre la base de los principios de beneficencia, no maleficencia, de precaución y de proporcionalidad, no se recomienda la incorporación de parches.(AU)

INTRODUCTION: Contraception is a right, being an obligation of the State to guarantee access to effective, safe and quality contraceptive methods. A health technology assessment was carried out on transdermal contraceptive patches. METHODS: A multidisciplinary and independent team appointed by the Provincial Biotechnology Committee of Neuquén searched for epidemiological and regulatory information and scientific evidence on efficacy, safety and adherence. It was analyzed and systematized following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and CASPe (Critical Appraisal Skills Programme Español) methodology. RESULTS: The only patch authorized for commercialization in Argentina releases 33.9 µg/day of ethinylestradiol and 203 µg/day of norelgestromin. Its package insert in Argentina, the US and Europe highlights that the risk of venous thromboembolic disease is twice as high compared to the contraceptive pills provided by the State. This is consistent with results from high-quality cohort studies. Patches provide similar short-term contraceptive efficacy, but with high dropout rates at follow-up. The World Health Organization has not included them in its list of essential medicines. Patches are more expensive than other available methods. DISCUSSION: Based on the principles of beneficence, non-maleficence, precaution and proportionality, the incorporation of patches is not recommended.(AU)

Treatment of postoperative localized neuropathic pain with topical 5% lidocaine. Case report / Tratamento de dor neuropática pós-operatória localizada com lidocaína tópica a 5%. Relato de caso

ABSTRACT BACKGROUND AND OBJECTIVES: Post-surgical neuropathic pain (NP) is an important clinic condition, with recurring pain and that may be a result of transection, contusion, nerve inflammation or stretching and lasting for 3-6 months. Having into consideration the prevalence of postoperative localized NP, its impact in quality of life of patients, its complexity of diagnosis and treatment and available treatment options, the aim of this report was to present efficacy, safety and tolerability outcomes of 5% lidocaine transdermal patch use as a single treatment or in combination with other therapeutic options by describing and analyzing four clinical cases. CASES REPORT: Four patients aged between 43 and 70 years old and complains of postoperative localized NP were managed with 5% lidocaine transdermal patch in prolonged treatment, with significant improvement in pain scores. CONCLUSION: The outcomes of the described cases revealed that postoperative localized NP management was successful with 5% lidocaine transdermal patch. Moreover, it was possible to observe that its association to other treatments (pharmacological or not) has proved efficacy with no negative impact the tolerability of the treatment or the patient routine and comfort.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor neuropática (DN) pós-operatória é um problema clínico relevante, com dor persistente, que pode ser resultado de transecção, contusão, alongamento ou inflamação do nervo, durando geralmente cerca de 3-6 meses após a cirurgia. Tendo em consideração a prevalência estimada da DN localizada pós-operatória, seu impacto na qualidade de vida dos pacientes, sua complexidade diagnóstica e terapêutica, e as opções de tratamento disponíveis, o presente estudo teve como objetivo apresentar os desfechos de eficácia, segurança e tolerabilidade do uso do emplastro de lidocaína a 5% nesta condição clínica, seja como fármaco isolado ou em combinação com outras classes terapêuticas. RELATO DOS CASOS: Quatro pacientes com idades entre 43 e 70 anos e com história de DN localizada pós-operatória foram manejados com emplastro de lidocaína a 5% em tratamento prolongado, com melhora significativa do nível de dor. CONCLUSÃO: Os resultados dos casos apresentados neste estudo revelam que o manejo da DN localizada pós-operatória foi eficaz com a utilização do emplastro de lidocaína a 5%. Além disso, foi possível observar que sua associação com outros tratamentos (farmacológicos ou não) mostrou-se efetiva, sem impactar negativamente a tolerabilidade do tratamento ou o conforto do paciente.

A Case of Acute Withdrawal Symptoms Due to Unplanned Interruption of Buprenorphine Transdermal Patch: With a Discussion Including Social Aspects of Home Medical Care Patients

Introduction: Since the commercial availability of buprenorphine extended-release transdermal patches (BTDP) from the early 2010’s, the therapeutic indications for opioids have widely expanded to include chronic benign diseases. We report a case of a home health care patient with acute opioid withdrawal symptoms due to self-interruption of BTDP. Case: An 84-year-old man using home health care services due to worsening of lumbar spinal canal stenosis had been receiving analgesia with a BTDP, a mixed opioid agonist/antagonist analgesic, for the preceding five months. Since the patient's spouse thought that his pain and symptoms were gradually improving, she secretly replaced the BTDP with an NSAID patch without informing the patient. About 50 hours later, the patient experienced a variety of symptoms, including frequent urination with incontinence every five minutes, watery diarrhea, sweating, decreased blood pressure, discomfort in the feet, and insomnia. Evaluation of the Clinical Opiate Withdrawal Score (COWS) by the home health care physician indicated a score of 12, corresponding to mild withdrawal symptoms. About 12 hours after symptom onset, the severe abnormalities were barely noticeable and completely disappeared after two days. Conclusion: Few previous case reports have described withdrawal symptoms due to rapid discontinuation of BTDP. In addition to the medical considerations, we report the social issues associated with onset of the condition in a home environment. Opioid use for non-cancer pain requires medication management from a different perspective than that for cancer pain.

In vitro transdermal drug permeation tests: a regulatory scenario evaluation

SUMMARY Introduction: The Transdermal Drug Delivery Systems (TDDS) could circumvent the inconveniences of oral administration, increasing treatment adhesion. Meanwhile, despite being highly widespread systems, there are discrepancies between the performance and quality control methodologies recommended by the leading regulatory agencies, which is an issue for the pharmaceutical industry. Aim: To identify and to compare the requirements for TDDS regulatory approval by important agencies, focusing on the in vitro release and drug permeation studies, which are crucial tests for the evaluation of safety, efficacy, and performance of these systems. Methods: The documents that regulate the scope of TDDS in FDA, EMA and Anvisa were analyze, as well as the contributions of OECD. In addition, an approaching regarding the pharmacopeial requirements was made regarding USA, Europe, and Brazil. Results and conclusion: Concerning the regulatory approval aspects, the FDA is reviewing its documents because the current guidance is not specific to transdermal systems. On the other hand, the EMA presents a unique guideline that includes specific requirements for TDDS. The USA and the European Pharmacopoeias have specific mentions to performance and quality control of TDDS, while the Brazilian Pharmacopoeia does not mention this dosage form. Recently, Anvisa published a guide, which helps Brazilian manufacturers concerning the tests required for the regulatory approval of a new TDDS. The launch of this standardized national statute associated with the use of a validated in vitro release and permeation tests represents a remarkable breakthrough regarding TDDS.

Introducción: los sistemas de administración de fármacos transdérmicos (TDDS) podrían sortear los inconvenientes de la administración por vía oral, aumentando la adherencia al tratamiento. Mientras tanto, a pesar de ser sistemas muy extendidos, existen discrepancias entre las metodologías de desempeño y control de calidad recomendadas por las principales agencias reguladoras, lo cual es un problema para la industria farmacéutica. Objetivo: identificar y comparar los requisitos para la aprobación regulatoria de TDDS por parte de las principales agencias reguladoras, enfocándose en los estudios de liberación in vitro y premiación de fármacos. Métodos: se analizaron los documentos que regulan el alcance de la TDDS en la FDA, EMA y Anvisa, así como los aportes de la OCDE. Además, se realizó un planteamiento sobre los requisitos de las farmacopeas de los Estados Unidos, Europa y Brasil. Resultados y conclusión: la FDA está revisando los aspectos de aprobación regulatoria porque la guía actual no es específica para los sistemas transdérmicos. Por otro lado, la EMA presenta una guía única que incluye requisitos específicos para TDDS. Las farmacopeas de los Estados Unidos e Europa tienen menciones específicas al rendimiento y control de calidad de TDDS, mientras que la Farmacopea brasileña no menciona esta forma de dosificación. Recientemente, Anvisa publicó una guía que ayuda a los fabricantes brasileños en cuanto a las pruebas requeridas para la aprobación regulatoria de un nuevo TDDS. El lanzamiento de este estatuto nacional estandarizado asociado con el uso de pruebas validadas de liberación y premiación in vitro representa un avance notable con respecto a TDDS.

Introdução: os sistemas de liberação transdérmica (SLT) são capazes de contornar as desvantagens da administração oral de medicamentos, aumentando a adesão ao tratamento. Entretanto, apesar de serem sistemas difundidos, existem discrepâncias entre as metodologias de desempenho e controle de qualidade recomendadas pelas agências regulatórias, dificultando o desenvolvimento destes pela indústria farmacêutica. Objetivo: identificar e comparar os requisitos para aprovação regulatória de SLT por importantes agências regulatórias, com foco nos estudos de liberação e permeação de fármacos in vitro, testes fundamentais para avaliação da segurança, eficácia e desempenho desses sistemas. Métodos: foram analisados os documentos que regulam o escopo dos SLT publicados pela FDA, EMA e Anvisa e as contribuições da OCDE. Além disso, foi realizada a abordagem sobre os requisitos farmacopeicos nos Estados Unidos, Europa e Brasil. Resultados e conclusão: FDA está revisando os aspectos de aprovação regulatória, pois os documentos atuais não são específicos para os SLT. Em contraponto, a EMA apresenta uma diretriz única que inclui requisitos específicos para estes sistemas. Em relação às farmacopeias, enquanto EUA e Europa apresentam recomendações específicas para desempenho e controle de qualidade dos SLT, a Farmacopeia brasileira não menciona esta forma farmacêutica. Recentemente, a Anvisa publicou um guia com os testes necessários para o registro destes sistemas. O lançamento de tal publicação, associado a ensaios devidamente validados representam um avanço notável no escopo regulatório dos SLT.

Development and optimization of metoclopramide containing polymeric patches: impact of permeation enhancers

Abstract The study is aimed to develop a monolithic controlled matrix transdermal patches containing Metoclopramide as a model drug by solvent casting method. Eudragit L100, Polyvinylpyrrolidone K-30, and Methylcellulose were used in different ratios and Polyethylene glycol 400 added as a plasticizer. Resulting patches were evaluated for their physicochemical characters like organoleptic characters, weight variation, folding endurance, thickness, swelling index, flatness, drug content, swelling index, percentage erosion, moisture content, water vapor transmission rate and moisture uptake. Formed patches were also evaluated through Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Scanning Electron Microscopy (SEM). Results of SEM unveiled smooth surface of drug-loaded patches. In-vitro dissolution studies were conducted by using dissolution medium phosphate buffer saline pH 7.4. Effect of natural permeation enhancers was elucidated on two optimized formulations (Z4 and Z9). Different concentrations (5%-10 %) of permeation enhancers i.e. Olive oil, Castor oil and Eucalyptus oil were evaluated on Franz diffusion cell using excised abdominal rat skin. Z4-O2 (Olive oil 10%) had enhanced sustain effect and flux value (310.72) close to the desired flux value. Z4-O2 followed Higuchi release model (R2= 0.9833) with non-fickian diffusion release mechanism (n=0.612)

Transdermal buprenorphine for acute postoperative pain: a systematic review / Uso da buprenorfina transdérmica na dor aguda pós-operatória: revisão sistemática

Background and objectives: Postoperative pain is still a major concern in several surgical procedures. Multimodal analgesia is best for postoperative pain management; however, opioid therapy is still the main treatment for pain after surgical procedures. Transdermal buprenorphine is a partial µ-agonist opioid widely used for chronic pain syndromes, with limited evidence for acute postoperative pain. A systematic review of studies examining transdermal buprenorphine for acute pain management after surgery was conducted. Contents: Data from PubMed, Embase, The Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL via EBSCOhost, and LILACS were reviewed, including randomized clinical trials that evaluated total postoperative pain, postoperative analgesic consumption, drug-related side effects and patient satisfaction with analgesia regimen. Data from nine studies (615 patients) were included in this review. Most studies initiated transdermal buprenorphine use 6 to 48 hours before surgery, maintaining use from 1 to 28 days after the procedure. Most studies showed lower or similar postoperative pain scores, postoperative analgesic consumption and patient satisfaction comparing buprenorphine to placebo, tramadol, celecoxib, flurbiprofen and parecoxib. The incidence of side effects varied between studies, with most showing no increase in drug-related side effects with buprenorphine use, except one study, which compared buprenorphine to oral tramadol, and one to transdermal fentanyl. However, most results were derived from evidence with an overall high or unclear risk of bias. Conclusions: Although more studies are necessary, initial results show that transdermal buprenorphine seems to be an effective and safe opioid choice for management of acute postoperative pain

Justificativa e objetivos: A dor pós-operatória ainda é uma queixa importante em vários procedimentos cirúrgicos. A analgesia multimodal é a melhor conduta para a dor pós-operatória, embora a terapia com opioides ainda seja o principal tratamento para a dor após procedimentos cirúrgicos. A buprenorfina transdérmica é um opioide agonista µ amplamente prescrito nas síndromes de dor crônica, mas com limitada evidência do seu uso para dor aguda no pós-operatório. Realizamos revisão sistemática de estudos que examinaram o papel da buprenorfina transdérmica no tratamento da dor aguda pós-operatória. Conteúdo: Revisamos os dados de PubMed, Embase, Registro Central de Ensaios Controlados Cochrane (CENTRAL), CINAHL via EBSCOhost e LILACS, incluindo estudos clínicos randomizados que avaliaram a dor pós-operatória total, consumo de analgésicos pós-operatórios, efeitos colaterais relacionados a medicamentos e satisfação do paciente com esquema de analgesia. Dados de nove estudos (615 pacientes) foram incluídos nesta revisão. A maioria dos estudos iniciou o uso transdérmico de buprenorfina 6 a 48 horas antes da cirurgia, mantendo o uso de 1 a 28 dias após o procedimento. A maioria dos estudos encontrou valores semelhantes ou menores para o escore de dor pós-operatória, consumo pós-operatório de analgésicos e satisfação do paciente quando a buprenorfina foi comparada ao placebo, tramadol, celecoxibe, flurbiprofeno e parecoxibe. A incidência de efeitos colaterais oscilou nos estudos, e a maioria não mostrou aumento de efeito colateral relacionado ao uso de buprenorfina, exceto em dois estudos, um que comparou buprenorfina ao tramadol oral e outro ao fentanil transdérmico. No entanto, a maioria dos resultados foi obtida a partir de evidências com um risco geral alto ou risco de viés impreciso. Conclusões: Embora sejam necessários mais estudos, os resultados iniciais mostram que a buprenorfina transdérmica parece ser uma forma de administração segura e efetiva de opioide no tratamento da dor aguda pós-operatória

Mechanistic insights of the controlled release capacity of polar functional group in transdermal drug delivery system: the relationship of hydrogen bonding strength and controlled release capacity

Background@#Hydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal patch. However, the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported, and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive (PSA) was not well understood. The present study shed light on this relationship.@*Methods@#Acrylate PSAs with amide group were synthesized by a free radical-initiated solution polymerization. Six drugs, , etodolac, ketoprofen, gemfibrozil, zolmitriptan, propranolol and lidocaine, were selected as model drugs. drug release and skin permeation experiments and pharmacokinetic experiment were performed. Partial correlation analysis, fourier-transform infrared spectroscopy and molecular simulation were conducted to provide molecular details of drug-PSA interactions. Mechanical test, rheology study, and modulated differential scanning calorimetry study were performed to scrutinize the free volume and molecular mobility of PSAs.@*Results@#Release rate of all six drugs from amide PSAs decreased with the increase of amide group concentrations; however, only zolmitriptan and propranolol showed decreased skin permeation rate. It was found that drug release was controlled by amide group through hydrogen bonding, and controlled release extent was positively correlated with hydrogen bonding strength.@*Conclusion@#From these results, we concluded that drugs with strong hydrogen bond forming ability and high skin permeation were suitable to use amide PSAs to regulate their release rate from patch.

A Comparative Study to Evaluate Efficacy of Fentanyl Transdermal Patch VS Ketoprofen Patch in Pain Control after Mandibular Third Molar Surgery

Background: Surgical removal of impacted lower third molars is a common oral surgical procedure, generally followed by moderate to severe postoperative pain. Transdermal drug delivery as a concept offers interesting possibilities for postoperative pain control. Aims and Objectives: to evaluate and compare the degree of post-operative analgesia, patient compliance and frequency of adverse events between transdermal ketoprofen patch and transdermal fentanyl patch following third molar extraction. Methods: Total 7 patients aged 18-65 years with impacted mandibular third molar teeth were included in the study. The study drugs transdermal patches of fentanyl and ketoprofen was applied one hour before the surgical procedure on the skin, preferably in an area devoid of any hair. The selected mandibular third molar tooth of either of the side was extracted in the first appointment using an aseptic protocol. Every patient was given a Verbal Pain Intensity and Pain Relief chart ( both 5- point scales with values 0-4 ) for assessing pain intensity and pain relief for all the three post-operative days. Results: During the first four hours of operative day, the difference observed between the two groups was not found to be statistically significant (p=0.881). Whereas during the first eight hours of operative day the difference observed between the two groups was not found to be statistically significant (p=0.141). During the first twelve hours of operative day, the difference observed between the two groups was not found to be statistically significant (p=0.276). At the end of operative day, the difference observed between the two groups was found to be statistically significant (p=0.048). Conclusion: Transdermal fentanyl patch was more effective for immediate pain relief than transdermal ketoprofen patch for pain control following removal of mandibular impacted third molars.

Anxious medico with nicotine patch: a case report

We often suffer more in our imaginations than in reality. Anxiety is a terrible experience, you could even have an attack and no one would even know most of the times because it is an inward thing. People do get anxious and experience this feeling most of the times in life. Up to an extent its normal as much as it can be controlled if not this unpleasant feeling overrules. We learn to combat this feeling as the age passes but it also depends on different environmental, social occupational factors and the level of stress to overcome can be difficult. Many non-pharmacological and pharmacological methods are available to combat anxiety disorder. Self-medications can be occupational hazard and is strongly entrenched within the culture of both physicians and medical students as an accepted way to buffer their work performance. We are reporting a case of an anxious medico self-medicated to combat anxiety.

Effect of Metallic Arraymicroneedle Pretreatment on Ramosetron Hydrochloride Paches in Transdermal Drug Delivery / 中国药学杂志

OBJECTIVE: To evaluate the effects of different pretreatment ways on microneedle onits penetration enhancing effect for ramosetron hydrochloride paches in microneedle-assisted transdermal drug delivery. METHODS: Skin penetration experiments were carried out using excised guinea pig skin. Microneedle pretreatment ways including needle type, needle length, needle acting force and acting time were taken as the influencing factors. The main effects and interaction effects of influencing factors in skin penetration enhancement were analyzed. RESULTS: Microneedle length had the most significant impact on drug skin penetration. When the length changed from 200 μm to 300 μm, the steady-state permeation rate and the cumulative permeation amount within 48 h displayed marked increase. Additionally, there was interaction between the penetration enhancing effects of the microneedle length and acting force. When the acting time and needle type were fixed and the microneedle length was 200 μm, no significantly different impacts occurred if the acting force varied between 3 and 5 N. However, if the microneedle length was 300 μm, the penetration enhancing effects became more significant when increasing acting force from 3 to 5 N. CONCLUSION: This studies suggeste that microneedle pretreatment ways may result in different effects on penetration of drugs through skin, and there may exist interaction effect between different microneedle pretreatment ways.This study provides a reference for the selection of microneedle pretreatment in microneedle-assisted transdermal drug delivery.

In Vitro Consistency Evaluation of Tulobuterol Patch and The Impact of Quality Standard Characteristics on Industrialization / 中国药学杂志

OBJECTIVE: To prepare of a torotrope transdermal patch for in vitro consistency evaluation and explor of the impact of quality standard characteristics on industrialization. METHODS: The tulobuterol transdermal patch was prepared with polyisobutylene B50, polybutene and petroleum resin as auxiliary excipients. The drug content in the sample was determined by high-performance liquid chromatography; in vitro consistency was evaluated by microscopy, differential thermal analysis, Fourier transform infrared spectroscopy, viscosity tester, dissolution Tester, and transdermal tester. The dissolution of the patch and its relationship with transdermal permeation, drug crystallization and in vitro release mechanism of the patch were studied in order to explore the influence of quality standard characteristics on industrialization. RESULTS: The self-made patch and the reference preparation have conformity in the drug content, drug crystallization, DSC, MATR, heat resistance, cold resistance, viscosity and shape. The dissolution tests were performed in medium of water and phosphate buffer (pH 7.4, 6.8, 4.0), and the corresponding f2 were 72.516, 94.840, 90.905, and 81.760. The average transdermal permeability ratio is 1.02 and the skin retention ratio is 0.88. The drug solubility is pH dependent while the in vitro dissolution is not sensitive to pH. The correlation between transdermal and dissolution in vitro is good. The in vitro release is affected by the composition of the excipients and the crystallization of the drug. CONCLUSION: The self-adhesive and the reference preparation have good consistency in vitro evaluation; the in vitro dissolution test can effectively reflect the transdermal permeation and absorption process of the drug in vitro. The drug crystallization evaluation index in the preparation is introduced to improve the quality control detection efficiency and quality assurance in the industrialization process. Research reference is provided for the consistency evaluation research, industrialization and quality standard improvement of this product.

Effect of traditional Chinese medicine enema combined with rhubarb acupoint in the treatment of severe acute pancreatitis complicated with paralytic ileus / 中国基层医药

Objective@#To observe the clinical effect of traditional Chinese medicine enema combined with rhubarb acupoint in the treatment of severe acute pancreatitis(SAP) complicated with paralytic ileus.@*Methods@#A total of 60 SAP patients complicated with paralytic ileus treated in the First People's Hospital of Huzhou from June 2015 to June 2017 were selected and randomly divided into two groups by random lottery method, with 30 cases in each group.The two groups were treated with routine anti-infection and rehydration.The control group was treated with traditional Chinese medicine enema combined with placebo, and the observation group was treated with traditional Chinese medicine enema combined with rhubarb on Shenque acupoint, and the two groups were treated for 7d.The recovery time of blood amylase, bowel sounds recovery time, first self defecation time, local complications and mortality were observed in the two groups.@*Results@#The recovery time of blood amylase, the recovery time of intestinal sound and the time of the first defecation were (8.87±2.30)d, (2.88±1.09)d and (3.51±1.32)d, respectively, which were significantly shorter than those of the control group [(10.29±2.01)d, (3.67±1.30)d and (4.57±1.41)d], the differences were statistically significant(t=-3.601, -3.607, -4.251, all P<0.001). The incidence rate of local complications in the observation group was 6.7%(2/30), which was significantly lower than 36.7%(11/30) in the control group(χ2=16.875, P<0.001), and there was no statistically significant difference in the mortality rate between the two groups(χ2=3.333, P=0.068).@*Conclusion@#The application of Chinese medicine enema combined with the acupoint of rhubarb in the treatment of SAP patients complicated with paralytic ileus can effectively promote the recovery of intestinal peristalsis, shorten the duration of paralytic intestinal obstruction, reduce the complications and improve the clinical effect.

Efficacy and Safety of Clonidine Transdermal Patch for Child Tic Disorders ：A Meta-analysis / 中国药房

OBJECTIVE： To systematically evaluate the efficacy and safety of Clonidine tansdermal patch for child tic disorders in children， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from Medline， Embase， Cochrane library， CNKI， VIP， CBM and Wanfang database， randomized controlled trials （RCTs） about Clonidine tansdermal patch （trial group） versus other therapies （control group， including placebo group， thiopride group， haloperidol group） for child tic disorders were collected from datbase estallishment to July 2018. The literatures met inclusion criteria were summarized. After quality evaluation with Cochrane system evaluation manual 5.1.0， Meta-analysis of reduction rate （amount） of YGTSS， the incidence of ADR and response rate was performed by using Rev Man 5.3 statistical software. Descriptive analysis was performed on indicators of groups that were unable to perform Meta-analysis. RESULTS： A total of 8 RCTs involving 1 320 patients were included. Among them， 2 RCTs involved placebo in control group； 2 RCTs involved thiopride， 3 RCTs involved haloperidol， and 1 RCT involved thiopride and haloperidol. Results of Meta-analysis showed that reduction rate of YGTSS in trial group were significantly higher than haloperidol group [MD＝21.94， 95％CI（21.03， 22.86）， P＜0.001]， but there was no statistical significance compared with thiopride group [MD＝10.66， 95％CI（－15.68， 37.00）， P＝0.43]. The incidence of adverse events （mainly including skin itching， redness， dry mouth， dizziness， decreased blood pressure， abnormal electrocardiogram） in trial group were significantly lower than thiopride group [OR＝0.42， 95％CI（0.22， 0.82）， P＝0.01] and haloperidol group [OR＝0.17， 95％CI（0.09， 0.32）， P＜0.001]， but there was no statistical significance compared with placebo group [OR＝0.61， 95％CI（0.29， 1.29）， P＝0.20]. There was no statistical significance in response rate of trial group compared with thiopride group [OR＝1.29，95％CI（0.38， 4.39）， P＝0.69] and haloperidol group [OR＝1.63， 95％CI（0.89， 2.96）， P＝0.11]. The results of descriptive analysis showed that reduction rate （amount） of YGTSS in trial group was significantly higher than that of placebo group （P＜0.05）， and response rate of trial group was significantly higher than that of placebo group （P＜0.01）. CONCLUSIONS： For child tic disorders in children， Clonidine tansdermal patch is better than placebo and haloperidol in reduction rate （amount） of YGTSS， and is similar to thiopride. Response rate of Clonidine tansdermal patch is better than that of placebo， and is similar to those of thiopride and haloperidol. The safety of Clonidine tansdermal patch is better than those of thiopride and haloperidol， and is similar to that of placebo.

Effect of traditional Chinese medicine enema combined with rhubarb acupoint in the treatment of severe acute pancreatitis complicated with paralytic ileus / 中国基层医药

Objective To observe the clinical effect of traditional Chinese medicine enema combined with rhubarb acupoint in the treatment of severe acute pancreatitis(SAP) complicated with paralytic ileus.Methods A total of 60 SAP patients complicated with paralytic ileus treated in the First People's Hospital of Huzhou from June 2015 to June 2017 were selected and randomly divided into two groups by random lottery method,with 30 cases in each group.The two groups were treated with routine anti-infection and rehydration.The control group was treated with traditional Chinese medicine enema combined with placebo,and the observation group was treated with traditional Chinese medicine enema combined with rhubarb on Shenque acupoint,and the two groups were treated for 7d.The recovery time of blood amylase,bowel sounds recovery time,first self defecation time,local complications and mortality were observed in the two groups.Results The recovery time of blood amylase,the recovery time of intestinal sound and the time of the first defecation were (8.87 ± 2.30) d,(2.88 ± 1.09) d and (3.51 ± 1.32) d,respectively,which were significantly shorter than those of the control group [(10.29 ± 2.01) d,(3.67 ± 1.30) d and (4.57 ± 1.41) d],the differences were statistically significant (t =-3.601,-3.607,-4.251,all P ＜ 0.001).The incidence rate of local complications in the observation group was 6.7％ (2/30),which was significantly lower than 36.7％ (11/30) in the control group(x2 =16.875,P ＜ 0.001),and there was no statistically significant difference in the mortality rate between the two groups (x2 =3.333,P =0.068).Conclusion The application of Chinese medicine enema combined with the acupoint of rhubarb in the treatment of SAP patients complicated with paralytic ileus can effectively promote the recovery of intestinal peristalsis,shorten the duration of paralytic intestinal obstruction,reduce the complications and improve the clinical effect.

Formulation Optimization of Rutaecarpine Transdermal Patch / 中国药学杂志

OBJECTIVE: To screen pressure sensitive adhesive system and penetration enhancer of rutaecarpine transdermal patch. METHODS: The patch was prepared by solvent evaporation method. The ratio between pressure sensitive adhesive (Eudragit E100), crosslinking agent (succinic acid) and plasticizer (dibutyl sebacate) of the rutaecarpine patch were screened through Box-Behnken design by using adhesion (stick power, shear strength, peel force) as the index. The ratio between pressure sensitive adhesives and chemical enhancers (azone and oleic acid) were screened by adhesion and permeation experiments in vitro using custom design, which were carried out by using improved Franz diffusion cells through excised mice skin. RESULTS: The optimized formulation of rutaecarpine transdermal patch consisted of 83% pressure sensitive adhesives (63.5% Eudragit E100, 5.5% succinic acid, 14% dibutyl sebacate), 10% azone, 6.4% oleic acid and 0.6% rutaecarpine. The stick power, shear strength, and peel force of the patch were 15 steel balls, (10.97 ± 0.32) h and (0.16 ± 0.02) kN•M-1, respectively. The cumulative permeation amount and permeation rate of the patch were (29.71 ± 1.19) μg•cm-2 and (1.36 ± 0.10) μg•cm -2•h -1, respectively. CONCLUSION: The optimized rutaecarpine patch show increased permeation and appropriate adhesion. This study provides the basis for future research.

Preparation and Evaluation in Vivo and in Vitro of Tulobuterol Crystal Reservoir Patch / 中国药学杂志

OBJECTIVE: To prepare the tulobuterol crystal reservoir patch, and to evaluate morphology, stability and crystallization factors of the crystal in the patch, adhesive force, dissolution, transdermal properties in vitro and the pharmacokinetics in rabbits. METHODS: The transdermal patch was prepared on the basis of drug recrystallization and characterized by morphology, stability and crystallization factors using microscope and adhesive force using initial adhesion tester, adhesion tester and peel tester. The dissolution and transdermal properties were evaluated by using the dissolution tester and transdermal tester. In addition, pharmacokinetics was studied using New Zealand rabbits as experimental animals. RESULTS: The drug crystals were evenly distributed in the form of filaments, which had average width of (4.4±1.8)μm and kept stable at 2-40 ℃. The crystallization in patches is affected by tulobuterol supersaturation and temperature. The adhesive force of patch was suitable and its dissolution matched standard which can be fitted by the Higuchi equation. In the diffusion cell in vitro, the drug penetrated through the skin in a Zero-order kinetic equation, and the cumulative penetration percentage and skin retention concentration were 92.04% and 10.36 μg·cm-2 with in 24 h. The pharmaceutic parameters showed that the tulobuterol blood concentration can be maintained within 24 h, whose tmax and ρmax were (6.67±3.06)h and (3.08±1.32) ng·mL-1, respectively. CONCLUSION: The tulobuterol crystal reservoir patch can be established by control of recrystallization conditions. The patch has good adhesive properties and sustained release characteristics in vitro and in vivo, which has the practical significance for further study.

Preparation of Guizhi Fuling transdermal patch / 中成药

AIM To prepare Guizhi Fuling transdermal patch.METHODS With kinds of pressure-sensitive adhesive and penetration enhancer,kind and consumption of solvent,drug loading as influencing factors,appearance,formability and viscidity of patch,extract dispersion as evaluation indices,single factor test was applied to optimizing the preparation.And subsequent in vitro transdermal absorption test was performed to investigate the steady-state permeation rates of paeoniflorin,cinnamic acid and paeonol onto rat skins.RESULTS The optimal conditions were determined to be Duro-Tak 87-2677 polyacrylate pressure-sensitive adhesive (matrix),1 ∶ 0.5 for ratio of extract to propanediol (solvent),3％ azone as a penetration enhancer,and 20％ for drug loading,the obtained transdermal patch demonstrated both ideal initial adhesion force and holding adhesion force.These three constituents' average transdermal rates were 34.32,1.684,72.90 μg/(cm2 · h) with the average release rates of 26.81,1.523,111.8 μg/(cm2 · h),respectively,whose in vitro transdermal permeation curves conformed to Higuchi equation.CONCLUSION Guizhi Fuling transdermal patch processed with simple and stable preparation technique exhibits good in vitro transdermal permeation performance.

Optimization of Phencynonate Hydrochloride Transdermal Patch Formulation by Box-Behnken Design-response Surface Methodology / 中国药房

OBJECTIVE:To optimize the formulation of Phencynonate hydrochloride transdermal patch. METHODS:Phencynonate hydrochloride transdermal patch was prepared by solvent evaporation method. Using 48 h accumulative transdermal volume as index,single factor test and Box-Behnken design-response surface methodology were used to optimize drug dosage,the amount of transdermal enhancers azone and pressure-sensitive adhesive,and evaluate the appearance,adhesion of the formulation prepared by the best prescription. RESULTS:The optimized formulation was as follows as 263 mg drug dosage,165 mg azone, 1.94 g pressure-sensitive adhesive and 1.6 g methanol. 48 h accumulative transdermal volume of prepared patch was(119.48 ± 2.95)μ g/cm2(n=5),related error of which to predicted value was 2.48%. The prepared patch showed smooth surface and incision,good adhesiveness. CONCLUSIONS:Phencynonate hydrochloride transdermal patch is prepared successfully,its accumulative transdermal volume is in agreement with predicted standard.

Terapia de reemplazo de nicotina / Nicotine replacement therapy

Resumen Todas las formas comercialmente disponibles de terapia de reemplazo de nicotina (TRN) (chicles, parche transdérmico, aerosol nasal, inhalador y tabletas sublinguales / lozenges) pueden ayudar a de dejar de fumar con éxito. TRN aumenta la tasa cesación en un 50 a 70%. La combinación de un parche de nicotina con una forma de administración rápida de TRN es más eficaz que un solo tipo de NRT. No hay diferencia en la eficacia entre TRN y bupropión, la combinación de NRT y bupropión es más efectiva que bupropión solamente. Los efectos de TRN son en gran parte independientes de la duración de la terapia, la intensidad del apoyo prestado o lugar en el que se ofreció. Según expertos chilenos, se puede usar TRN en adolescentes, en forma de chicles de 2 mg asociado a terapia conductual. Si una embarazada expresa un claro deseo de recibir TRN, se sugiere (i) discutir con ella los riesgos y beneficios asociados, (ii) utilizarla sólo si falla la cesación con medidas no farmacológicas y (iii) utilizar el criterio profesional al decidir si ofrecer la prescripción de TRN, tomando en cuenta el nivel de adicción de la embarazada y la presencia de comorbilidades. Estos fármacos existen en Chile, pero no están hasta el momento disponibles en el sistema público de salud.

All commercially available forms of nicotine replacement therapy (NRT) (gum, transdermal patch, nasal spray, inhaler and sublingual tablets/pills) can help to quit smoking successfully. NRT increases the cessation rate by 50 to 70%. The combination of a nicotine patch with a rapid dosage form of NRT is more effective than a single type of NRT. There is no difference in efficacy between NRT and bupropion, the combination of NRT and bupropion is more effective than bupropion alone. The effects are largely independent of the duration of therapy, the intensity of the support provided or the setting in which the NRT was offered. According to Chilean experts, NRT can be used in adolescents, as chewing gum 2 mg adding behavioral therapy. If a pregnant woman expresses a clear desire to use NRT, it is suggested (i) discuss the associated risks and benefits with her, (ii) use it only if the cessation fails with non-pharmacological measures and iii) use the professional approach when deciding whether to offer the prescription of NRT, considering the level of addiction of the pregnant woman and the presence of comorbidities. TRN exists in Chile, but is not currently available in the public health system.