Propofol is an intravenously administered, hypnotic and short- acting pharmaceutical. One common sideeffect (>1:10) and therefore a disadvantage with propofol is the local pain that arise when the initial injection is given. Why the pain arise is not clearly understood. A majority of different pharmacological treatments, different doses and combinations, alternative administrations methods and physical interventions have been tried to reduce the pain when injection of propofol is given. One important task for the nurse is to relieve pain for patients. It is important for all patients to be painless and not experience discomfort caused by procedure in health care. The purpose of this study was to examine if administration of lidocaine and/ or remifentanil could in connection with injection of propofol reduce pain incidence and intensity at the injection. A literature study based on twenty-eight scientific articles was conducted. The result shows that a combination of lidocaine andremifentanil give the best pain relief. Howewer there is no difference in propofolinduced injection pain when lidocaine or remifentanil alone is compared. Other factors that could affect injection pain are use of a tourniquet which enhances the pain reduction, but the time that the tourniquet is applied is not decisive. The placement of the iv-catheter should be in the largest vein possible. By using this knowledge the incidence and intensity of pain could be reduced with drugs commonly used in Swedish aneasthetic care. Thereby patients' suffering could also be reduced.

Made available in DSpace on 2014-06-11T19:22:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2002Bitstream added on 2014-06-13T19:27:34Z : No. of bitstreams: 1 mannarino_r_me_botfm.pdf: 1143230 bytes, checksum: e78de0e8beeaacc11674b6664d6aa357 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A vantagem da anestesia injetável é a facilidade de produzir os componentes da anestesia (inconsciência, analgesia, relaxamento muscular e proteção neurovegetativa) com doses definidas dos diversos fármacos. Existem controvérsias sobre as doses de propofol necessárias para prover analgesia para realização de cirurgias. Objetivaram-se definir as taxas mínimas de infusão do propofol isoladamente e em associação com a lidocaína para anestesia intravenosa em cães, e a possível potencialização analgésica da lidocaína, avaliando-se os efeitos cardiovasculares e grau de hipnose. As DE50 do propofol e propofol associado a lidocaína foram calculadas em 10 cães (12,85 l 1,22 kg), sem raça definida, anestesiados 2 vezes com intervalo de 15 dias. G1: indução anestésica com propofol (6 mg/kg/iv) e manutenção inicial na velocidade de 0,7 mg/kg/min. G2: indução anestésica com propofol (6 mg/kg) e lidocaína (1,5 mg/kg) e manutenção inicial com propofol (0,7 mg/kg/min) e lidocaína em velocidade constante (0,25 mg/kg/min). A analgesia foi avaliada através do pinçamento de membrana interdigital dos membros posteriores e da ponta da cauda por 15 (quinze) segundos. De acordo com a resposta, a velocidade foi aumentada ou diminuída em 0,05 mg/kg/min, verificando-se a analgesia 10 (dez) minutos após até a determinação da velocidade na qual não havia respostas aos dois estímulos. Esta velocidade foi mantida por mais 2 (duas) mensurações. Em não havendo resposta era considerada a DE50. A média entre as velocidades (com e sem resposta) foi utilizada na determinação da taxa de infusão mínima de cada grupo. Esta DE50 foi utilizada na 2o etapa. Doze cães (12,28 l 1,37 kg) foram divididos em 2 grupos de seis. G3: indução anestésica com 6 mg/kg de propofol e manutenção... / There is a controversy on the doses of propofol to produce sufficient surgical analgesia. This study aimed to define the minimum infusion rate of propofol and propofol combined to lidocaine for IV anesthesia in dogs. The ED50 of propofol and propofol combined with lidocaine was calculated in 10 dogs, weighing 12.85 l 1.22 kg, anesthetized twice with a interval of 15 days. Anesthesia was induced (6 mg/kg/iv) and maintained with propofol (0.7 mg/kg/min.) (G1) and induced with propofol (6 mg/kg) and lidocaine (1.5 mg/kg) and maintained with propofol (0.7 mg/kg/min) and lidocaine (0.25 mg/kg/min) (G2). Analgesia was investigated by tail clamping and podal reflex. The infusion rate was increased or reduced in 0.05 mg/kg/min, until no painful response was observed. The infusion rate was maintained for more 2 (two) evaluations, with a 10 minutes interval and this rate was considered the DE50 of propofol. The mean infusion rate between no pain response and positive response was considered the mean minimal infusion rate and was used in the second part of the study. Other 12 dogs (12.28 l 1.37 kg) were divided in 2 groups of 6 animals. G3 was treated with the same protocol as G1 and G4 as G2, with the propofol infusion rates previously calculated. Anesthesia was maintained for 2 hours. Hemodynamic and respiratory variables as well as BIS and temperature were measured during anesthesia. There was a smaller cardiovascular depression and greater vascular resistance and acidosis in animals treated with propofol and lidocaine. The BIS was maintained between 40 and 60 in both groups. Lidocaine potentiated in 21% the analgesia produced by propofol. The minimum infusion rate of propofol was 1.25 mg/kg/min when used alone and 0.985 mg/kg/min when combined to lidocaine. Lidocaine potentiated hypnosis and analgesia produced by propofol and minimized the cardiovascular depression, increasing recovery.

Orientador: Stelio Pacca Loureiro Luna / Resumo: A vantagem da anestesia injetável é a facilidade de produzir os componentes da anestesia (inconsciência, analgesia, relaxamento muscular e proteção neurovegetativa) com doses definidas dos diversos fármacos. Existem controvérsias sobre as doses de propofol necessárias para prover analgesia para realização de cirurgias. Objetivaram-se definir as taxas mínimas de infusão do propofol isoladamente e em associação com a lidocaína para anestesia intravenosa em cães, e a possível potencialização analgésica da lidocaína, avaliando-se os efeitos cardiovasculares e grau de hipnose. As DE50 do propofol e propofol associado a lidocaína foram calculadas em 10 cães (12,85 l 1,22 kg), sem raça definida, anestesiados 2 vezes com intervalo de 15 dias. G1: indução anestésica com propofol (6 mg/kg/iv) e manutenção inicial na velocidade de 0,7 mg/kg/min. G2: indução anestésica com propofol (6 mg/kg) e lidocaína (1,5 mg/kg) e manutenção inicial com propofol (0,7 mg/kg/min) e lidocaína em velocidade constante (0,25 mg/kg/min). A analgesia foi avaliada através do pinçamento de membrana interdigital dos membros posteriores e da ponta da cauda por 15 (quinze) segundos. De acordo com a resposta, a velocidade foi aumentada ou diminuída em 0,05 mg/kg/min, verificando-se a analgesia 10 (dez) minutos após até a determinação da velocidade na qual não havia respostas aos dois estímulos. Esta velocidade foi mantida por mais 2 (duas) mensurações. Em não havendo resposta era considerada a DE50. A média entre as velocidades (com e sem resposta) foi utilizada na determinação da taxa de infusão mínima de cada grupo. Esta DE50 foi utilizada na 2o etapa. Doze cães (12,28 l 1,37 kg) foram divididos em 2 grupos de seis. G3: indução anestésica com 6 mg/kg de propofol e manutenção... (Resumo completo clicar acesso eletrônico abaixo) / Abstract: There is a controversy on the doses of propofol to produce sufficient surgical analgesia. This study aimed to define the minimum infusion rate of propofol and propofol combined to lidocaine for IV anesthesia in dogs. The ED50 of propofol and propofol combined with lidocaine was calculated in 10 dogs, weighing 12.85 l 1.22 kg, anesthetized twice with a interval of 15 days. Anesthesia was induced (6 mg/kg/iv) and maintained with propofol (0.7 mg/kg/min.) (G1) and induced with propofol (6 mg/kg) and lidocaine (1.5 mg/kg) and maintained with propofol (0.7 mg/kg/min) and lidocaine (0.25 mg/kg/min) (G2). Analgesia was investigated by tail clamping and podal reflex. The infusion rate was increased or reduced in 0.05 mg/kg/min, until no painful response was observed. The infusion rate was maintained for more 2 (two) evaluations, with a 10 minutes interval and this rate was considered the DE50 of propofol. The mean infusion rate between no pain response and positive response was considered the mean minimal infusion rate and was used in the second part of the study. Other 12 dogs (12.28 l 1.37 kg) were divided in 2 groups of 6 animals. G3 was treated with the same protocol as G1 and G4 as G2, with the propofol infusion rates previously calculated. Anesthesia was maintained for 2 hours. Hemodynamic and respiratory variables as well as BIS and temperature were measured during anesthesia. There was a smaller cardiovascular depression and greater vascular resistance and acidosis in animals treated with propofol and lidocaine. The BIS was maintained between 40 and 60 in both groups. Lidocaine potentiated in 21% the analgesia produced by propofol. The minimum infusion rate of propofol was 1.25 mg/kg/min when used alone and 0.985 mg/kg/min when combined to lidocaine. Lidocaine potentiated hypnosis and analgesia produced by propofol and minimized the cardiovascular depression, increasing recovery. / Mestre

O Objetivo deste estudo controlado e duplo-cego foi avaliar os efeitos cardiovasculares induzidos pelo bloqueio pterigomandibular com o anestésico local cloridrato de lidocaína 2%, associado à epinefrina, seguido da administração de ansiolítico (midazolam 15mg) ou placebo, para realização de cirurgia de colocação de implantes dentários inferiores bilaterais, em 22 pacientes (13 mulheres 9 homens). Os parâmetros cardiovasculares Pressão Arterial Sistólica (PAS), Diastólica (PAD), Média (PAM) e Freqüência Cardíaca (FC) foram monitorados pelos métodos oscilométrico e fotopletismográfico. Os valores médios foram registrados a cada minuto e de forma contínua durante as etapas do experimento da seguinte forma: Fase 0 Período basal; Fase 1 Anestesia local; Fase 2 incisão; Fase 3 perfuração; Fase 4 colocação dos implantes; Fase 5 sutura; Fase 6 período final. Os indivíduos que receberam midazolam não apresentaram alterações de PAS, PAD, PAM e FC significativas (p>0,01) comparada ao placebo. Ocorreram alterações significantes dos valores para o grupo que recebeu placebo e dos valores médios do grupo que receberam midazolam na freqüência cardíaca / The purpose of this controlled and double-blind trial was to evaluate cardiovascular effects induced by pterigomandibular block of local anesthetic (LA) 2 % lidocaína hydrochloride with epinephrine, followed administration of benzodiazepine (midazolam 15mg on hour prior) or placebo during the surgical phase of placement of the lower bilateral dental implant in 22 normotensive outpatients (13 female and 9 male). The cardiovascular parameters systolic (SP), diastolic (DP) and mean (MP) pressures and heart rate (HR) were monitored by oscillometric and photopletismographic methods in 06 clinical phases during the procedure. The mean values were recorded every minute and in a continuous way during the phases of the experiment following the sequence: phase 0 basal period; phase 1 - anesthesia local; phase 2 mucoperiostal flap; phase 3 perforation; phase 4 placement of dental implants; phase 5 suture; phase 6 the end period. The group with received midazolam didnt induce significant SP, DP, MP and HR changes (p>0.01) compared to placebo. Significantly higher values in placebo group and mean values in midazolam group in heart-frequency were observed.

Os equinos são comumente anestesiados com agentes voláteis em procedimentos cirúrgicos acima de 60 minutos, resultando em depressão cardiovascular dosedependente, contribuindo para uma alta taxa de mortalidade. Sendo assim, este estudo objetivou determinar se o fentanil, em infusão contínua, seria capaz de diminuir a fração expirada de isoflurano, promovendo estabilidade cardiovascular transoperatória e uma melhor recuperação após cirurgia de artroscopia, em comparação à infusão de lidocaína ou quetamina, durante a manutenção da anestesia com isoflurano. Para tanto foram utilizados 20 equinos de 3 a 8 anos e pesando 350 a 500kg, submetidos a cirurgia de artroscopia em decúbito dorsal. Os animais foram divididos aleatoriamente em 4 grupos: GL (1,5 mg/kg em bolus e infusão de 0,15mg/kg/min) ; GQ (2mg/kg em bolus e infusão de 0,2mg/kg/min); GF (7µg/kg em bolus e infusão de 0,7µg/kg/min) e GI que não recebeu infusão de nenhum fármaco adjuvante. Foram avaliados os parâmetros cardiovasculares (FC, PAM, PAS e PAD), ventilatórios e de oxigenação (PaO2, PaCO2, Compl e Rva), fração expirada de isoflurano [ISSO](Fexp%), e qualidade de recuperação. Em relação à [ISSO] (Fexp%) as maiores quedas foram observadas no momento 30bolus em todos os grupos, que utilizaram adjuvantes, comparados ao momento basal sendo, GL (1,50 para 0,90%) GQ (1,44 para 0,96%) e GF (1,32 para 0,96%). Observou-se que após 15 minutos da interrupção da infusão contínua de fentanil e lidocaína a fração expirada de isoflurano foi aumentada GL 25% e GF 45%. Apesar de não ter havido diferença estatística, o GF apresentou escore de recuperação menor 16,8 pontos, GL 24,6; GQ 30,0 e GI 31,8 pontos. Conclui-se então que o uso do fentanil foi capaz de reduzir a fração expirada de isoflurano em até 43%, não observando qualquer efeito colateral no momento da recuperação após re-sedação com xilazina 0,5mg/kg. / Volatile anesthetics are commonly used in horse anesthesia in surgical procedures over 60 minutes, resulting in a dose-dependent cardiovascular depression, contributing to a high mortality rate. Thus, the aimed this study was determine whether fentanyl continuous rate infusion would be able to reduce end tidal isoflurane, promoting intraoperative cardiovascular stability and a better recovery after arthroscopic surgery, when compared to lidocaine or ketamine infusion during maintenance of anesthesia with isoflurane. Therefore, 20 horses aging 3-8 years and weighing 350 to 500 kg underwent arthroscopic surgery in dorsal recumbence. The animals were randomly divided into four groups: GL (1.5 mg/kg bolus and 0.15 mg/kg/min infusion rate of lidocaine), GQ (2 mg/kg bolus and 0.2 mg/kg/min infusion of ketamine); GF (7µg/kg bolus and 0.7 mg/kg/min infusion rate of fentanyl) and GI did not receive any adjuvant infusion. Cardiovascular parameters (HR, MBP, SBP and DBP), ventilatory and oxygenation (PaO2, PaCO2, Cst and Rva), end tidal isoflurano [ISO] (Fexp%), and quality of recovery were evaluated. Regarding [ISO] (Fexp%) the highest decreases were observed at the time 30bolus in all groups with adjuvants, in comparison to base line -GL (1.50 to 0.90%) GQ (1.44 to 0.96 %) and GF (1.32 to 0.96%). At 15 minutes after the end of continuous rate infusion of fentanyl and lidocaine, expired fraction of isoflurane was increased 25% for GL and 45% for GF. Although there was no statistical difference, GF showed lower recovery score - 16.8 points, while 24.6 for GL, 30.0 for GQ and 31.8 points for GI. In conclusion, fentanyl was able to reduce end tidal isoflurane to 43%, with no side effects at recovery time after re-sedation with xylazine 0.5 mg / kg.

<p>Propofol is an intravenously administered, hypnotic and short- acting pharmaceutical. One common sideeffect (>1:10) and therefore a disadvantage with propofol is the local pain that arise when the initial injection is given. Why the pain arise is not clearly understood. A majority of different pharmacological treatments, different doses and combinations, alternative administrations methods and physical interventions have been tried to reduce the pain when injection of propofol is given. One important task for the nurse is to relieve pain for patients. It is important for all patients to be painless and not experience discomfort caused by procedure in health care. The purpose of this study was to examine if administration of lidocaine and/ or remifentanil could in connection with injection of propofol reduce pain incidence and intensity at the injection. A literature study based on twenty-eight scientific articles was conducted. The result shows that a combination of lidocaine andremifentanil give the best pain relief. Howewer there is no difference in propofolinduced injection pain when lidocaine or remifentanil alone is compared. Other factors that could affect injection pain are use of a tourniquet which enhances the pain reduction, but the time that the tourniquet is applied is not decisive. The placement of the iv-catheter should be in the largest vein possible. By using this knowledge the incidence and intensity of pain could be reduced with drugs commonly used in Swedish aneasthetic care. Thereby patients' suffering could also be reduced.</p>

Background: In order to perform cataract surgery, adequate dilatation of the pupil is essential. This is traditionally achieved by preoperative topical mydriatic eye-drops, commonly cyclopentolate and phenylephrine. This routine has several disadvantages. First, the slow penetration through the cornea delays the onset of mydriasis. Second, the limited bioavailability of topically administered substances with significant systemic absorption may increase the risk for systemic side effects. Third, even if good mydriasis is achieved initially with topical mydriatics (TM), the effect tends to wear off during surgery. In relation to cataract surgery a transient postoperative corneal oedema is sometimes noted, indicating effects on the corneal endothelial pump function. These effects have been ascribed to ultrasonic or mechanical trauma from the phacoemulsification procedure. Corneal endothelial cell loss (ECL) is a commonly studied variable, not least because it is associated with the long-term risk for corneal decompensation. But, there has been a debate whether postoperative corneal swelling after phacoemulsification cataract surgery correlates to ECL. Aims: To evaluate an alternative mydriatic regimen for phacoemulsification cataract surgery: intracameral injection of mydriatics mixed with lidocaine (ICM). Additionally, to determine the correlation between early transient postoperative corneal oedema and permanent ECL after phacoemulsification cataract surgery. Methods: Pupil dilatation with ICM (150 µl of lidocaine 1%, phenylephrine 1.5%, and cyclopentolate 0.1%) was compared to TM (phenylephrine 10% and cyclopentolate 1%) prior to cataract surgery. Additionally, two ICM-groups were randomized to receive either 0.6 µg/ml epinephrine added to the irrigating balanced salt solution or no epinephrine in the irrigation solution. Furthermore, two randomized ICM-groups, with or without cyclopentolate, were analyzed. The patients planned for cataract surgery were examined with ultrasonic pachymetry, specular microscope endothelial photography and Orbscan II slit-scan tomography pre- and postoperatively. Results: With ICM, mydriasis reached 95 ± 3% of its final value within 20 seconds. In the ICM-group, the pupils were smaller than in the TM-group (mean 6.7 ± 1.0 mm versus 7.7 ± 1.0 mm, P&lt;.001), but did not contract intraoperatively as the TM pupils did. Conversely, with ICM the pupil sizes generally increased during the cataract procedures. This increase was significantly greater without epinephrine in the irrigating solution (13 ± 19% versus 4 ± 14%; p = 0.02). No significant differences in pupil sizes were observed between the patients who were given ICM with or without cyclopentolate. The central corneal swelling at the first postoperative day was strongly correlated to the central ECL at 3 months, R2 = 0.785, P &lt; 0.001. Conclusions: ICM is a rapid and safe alternative to TM in phacoemulsification cataract surgery. An irrigating solution without epinephrine can safely be used with ICM. Cyclopentolate, administrated intracamerally, has no immediate additive mydriatic effect to intracameral lidocaine combined with phenylephrine. The degree of permanent corneal endothelial damage in cataract surgery is reflected in the degree of early postoperative corneal swelling.

BACKGROUND: Pain intensity, functional status and beliefs and attitudes towards pain are dynamic elements involved in the experience of chronic pain. Lidocaine infusion (LI) is a therapeutic intervention used to relieve pain. OBJECTIVES: The primary objective of this study was to determine if people with chronic pain who received LI and reported a decrease in pain intensity at 4 days post-infusion differed from those who did not report a decrease in pain intensity with respect to the following: a) baseline beliefs and attitudes towards pain; b) changes in belief and attitudes towards pain; c) and changes in functional status. This study also investigated if these differences were associated with being a novel or repeat LI user. A secondary objective was to estimate the sample size required for a larger study. METHODS: This project was an exploratory study. Thirty-three subjects were monitored for pain intensity using the Visual Analogue Scale (VAS) just before the infusion, and then at four days, two weeks, and three weeks after the infusion. The subjects were separated into groups depending on the criteria of whether or not they had: a) criterion-based pain intensity decrease or not on the fourth day post infusion, and b) received a previous LI or not. Since no subjects who received their first LI reported pain intensity decrease four days later, three groups emerged from this classification: first time LI users with no pain decrease, repeat LI users with no pain decrease, and repeat LI users with pain decrease. The subjects completed two self-administered questionnaires the Survey of Pain Attitudes (SOPA-32) and the Short Musculoskeletal Function Assessment (SMFA) - before the infusion, and at two and three weeks post-infusion. The most important change at two or three weeks post-infusion was used for comparison purposes. RESULTS: No significant changes in function (SMFA) were found. However, changes in specific beliefs and attitudes towards pain (SOPA-32) were associated with the group variable as follows: 1) All three groups showed a significantly stronger belief that 'others, especially family members, should be solicitous in response to their experience of pain' after the infusion. 2) Those who received their first LI and did not report pain intensity decrease also showed a significantly stronger belief that 'medications are an appropriate treatment for chronic pain' after the infusion. 3) Subjects who had previous LI and did not report pain intensity decrease were the only ones to believe significantly less that 'medications are an appropriate treatment for chronic pain' and more 'in a medical cure for their pain problem' after the infusion. 4) Subjects who had previous LI and did report pain intensity decrease had a significantly stronger belief in the appropriateness of medications and that 'that they should avoid exercise' after the infusion. 5) Finally, subjects who believed more that 'medications are an appropriate treatment for chronic pain' and less 'that they should avoid exercise' at baseline, had significantly higher chances of experiencing decrease in pain intensity 4 days after a LI. CONCLUSION: The impact of a LI on the individuals' beliefs and attitudes towards pain differs depending if their pain intensity decreased or not four days after the infusion, and if they had previous LI or not. By contrast, their pre-infusion beliefs and attitudes profile impacts on the efficacy of this intervention. Because of the small sample size, the heterogeneity of the subjects in terms of the localization of their pain, and our choice of measurement tool, it is not possible to determine if LI impacts on function. Nevertheless, this exploratory study generated some novel observations and questions that are of great interest for future research. A particular question of interest would be to determine if repeated LI fosters a more passive attitude towards pain management. It was also determined that a sample size of 70 subjects per group would be necessary for future research on this question. / Keywords: Chronic pain, lidocaine, beliefs and attitudes towards pain, function, pain intensity.

Local anaesthetics are used regularly in the medical world for a variety of different procedures. Topical anaesthetics are used largely in minor skin breaking procedures, laceration repair and minor surgical procedures such as laryngoscopy, oesophagoscopy or urethroscopy (Franchi et al., 2008:186e1). The topical means of application of a local anaesthetic is non-invasive and painless that results in a good patient acceptability profile (Little et al., 2008:102). An existing commercial topical anaesthetic product contains a eutectic mixture of the amide-type local anaesthetics lidocaine hydrochloride (HCl) and prilocaine hydrochloride (HCl). This commercial product takes up to an hour to produce an anaesthetic effect. This is considered as a disadvantage in the use of topical anaesthetics, an hour waiting time is not always ideal in certain medical circumstances (Wahlgren & Quiding, 2000:584). This study compared the lag times, transdermal and topical delivery of lidocaine HCl and prilocaine HCl from four different semi-solid formulations with the inclusion of a current commercial product. One of the formulated semi-solid formulations included Pheroid™ technology, a novel skin-friendly delivery system developed by the Unit for Drug Research and Development at the North-West University, Potchefstroom Campus, South Africa. The skin is the body’s first line of defence against noxious external stimuli. It is considered the largest organ in the body with an intensive and complex structure. It consists of five layers with the first outer layer, the stratum corneum, the most impermeable (Williams, 2003:1). The stratum corneum has excellent barrier function characteristics and is the cause for the time delay in the transdermal delivery of active pharmaceutical ingredients (API) (Barry, 2007:569). Local anaesthetics need to penetrate all the epidermal skin layers in order to reach their target site, the dermis. Skin appendages as well as blood vessels and skin nerve endings are located in the dermis. Local anaesthetics have to reach the free nerve endings in the dermis in order to cause a reversible block on these nerves for a local anaesthetic effect (Richards & McConachie, 1995:41). Penetration enhancement strategies for the transdermal delivery of lidocaine and prilocaine have been investigated and include methods like liposomal entrapment (Franz-Montan et al., 2010; Müller et al., 2004), micellisation (Scherlund et al., 2000), occlusive dressing (Astra Zeneca, 2006), heating techniques (Masud et al., 2010) and iontophoresis (Brounéus et al., 2000). The Pheroid™ delivery system has improved the transdermal delivery of several compounds with its enhanced entrapment capabilities. Pheroid™ consists mainly of unsaturated essential fatty-acids, non-harmful substances that are easily recognised by the body (Grobler et al., 2008:285). The morphology and size of Pheroid™ is easily manipulated because it is a submicron emulsion type formulation which provides it with a vast flexibility profile (Grobler et al., 2008:284). Vesicular entrapment was used to entrap lidocaine HCl and prilocaine HCl in the Pheroid™ and incorporated into an emulgel formulation. An emulgel without the inclusion of Pheroid™ was formulated for comparison with the Pheroid™ emulgel as well as with a hydrogel. Pheroid™ solution was prepared and compared to a phosphate buffer solution (PBS) without Pheroid™, both containing lidocaine HCl and prilocaine HCl as APIs. Franz cell type transdermal diffusion studies were performed on the four semi-solid formulations (emulgel, Pheroid™ emulgel, hydrogel and the commercial product) and two solutions (PBS and Pheroid™). The diffusion studies were performed over a 12 h period followed by the tape stripping of the skin after each diffusion study. Caucasian female abdominal skin was obtained with consent from the donors. The skin for the diffusion cells were prepared by using a Zimmer Dermatome®. PBS (pH 7.4) was prepared as the receptor phase of the diffusion studies. The receptor phase was extracted at certain pre-determined time intervals and analysed with high performance liquid chromatography (HPLC) to determine the amount of API that had traversed the skin. Stratum corneum-epidermis samples and epidermis-dermis samples were prepared and left over night at 4 °C and analysed the next day with HPLC. This was done to determine the amount of API that accumulated in the epidermis-dermis and the amount of API that were left on the outer skin layers (stratum corneum-epidermis). The results from the Franz cell diffusion studies indicated that the emulgel formulation without Pheroid™ shortened the lag time of lidocaine HCl and that the emulgel formulated with Pheroid™ shortened the lag time of prilocaine HCl, when compared to the commercial product. Pheroid™ did not enhance the flux of lidocaine HCl and prilocaine HCl into the skin. The hydrogel formulation demonstrated a high transdermal flux of prilocaine HCl due to the hydrating effect it had on the stratum corneum. The commercial product yielded high flux values for both APIs but it did not result in a high concentration of the APIs delivered to the epidermis-dermis. Pheroid™ technology did, however, enhance the epidermal-dermal delivery of lidocaine HCl and prilocaine HCl into the skin epidermis-dermis. The stability of the emulgel formulation, Pheroid™ emulgel formulation and the hydrogel formulation was examined over a 6 month period. The formulations were stored at 25 °C/60% RH, 30 °C/60% RH and 40 °C/75% RH. The API concentration, mass, pH, zeta potential, particle size, viscosity and visual appearance for each formulation at the different storage conditions were noted and compared at month 0, 1, 2, 3 and 6 to determine if the formulations remained stable for 6 months. The results obtained from the stability study demonstrated that none of the formulations were stable for 6 months. The emulgel remained stable for the first 3 months. At 6 months, large decreases in API concentration and pH occurred which could cause a loss of anaesthetic action in the formulations. The Pheroid™ emulgel formulation did not remain stable for 6 months. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.

Local anaesthetics are used regularly in the medical world for a variety of different procedures. Topical anaesthetics are used largely in minor skin breaking procedures, laceration repair and minor surgical procedures such as laryngoscopy, oesophagoscopy or urethroscopy (Franchi et al., 2008:186e1). The topical means of application of a local anaesthetic is non-invasive and painless that results in a good patient acceptability profile (Little et al., 2008:102). An existing commercial topical anaesthetic product contains a eutectic mixture of the amide-type local anaesthetics lidocaine hydrochloride (HCl) and prilocaine hydrochloride (HCl). This commercial product takes up to an hour to produce an anaesthetic effect. This is considered as a disadvantage in the use of topical anaesthetics, an hour waiting time is not always ideal in certain medical circumstances (Wahlgren & Quiding, 2000:584). This study compared the lag times, transdermal and topical delivery of lidocaine HCl and prilocaine HCl from four different semi-solid formulations with the inclusion of a current commercial product. One of the formulated semi-solid formulations included Pheroid™ technology, a novel skin-friendly delivery system developed by the Unit for Drug Research and Development at the North-West University, Potchefstroom Campus, South Africa. The skin is the body’s first line of defence against noxious external stimuli. It is considered the largest organ in the body with an intensive and complex structure. It consists of five layers with the first outer layer, the stratum corneum, the most impermeable (Williams, 2003:1). The stratum corneum has excellent barrier function characteristics and is the cause for the time delay in the transdermal delivery of active pharmaceutical ingredients (API) (Barry, 2007:569). Local anaesthetics need to penetrate all the epidermal skin layers in order to reach their target site, the dermis. Skin appendages as well as blood vessels and skin nerve endings are located in the dermis. Local anaesthetics have to reach the free nerve endings in the dermis in order to cause a reversible block on these nerves for a local anaesthetic effect (Richards & McConachie, 1995:41). Penetration enhancement strategies for the transdermal delivery of lidocaine and prilocaine have been investigated and include methods like liposomal entrapment (Franz-Montan et al., 2010; Müller et al., 2004), micellisation (Scherlund et al., 2000), occlusive dressing (Astra Zeneca, 2006), heating techniques (Masud et al., 2010) and iontophoresis (Brounéus et al., 2000). The Pheroid™ delivery system has improved the transdermal delivery of several compounds with its enhanced entrapment capabilities. Pheroid™ consists mainly of unsaturated essential fatty-acids, non-harmful substances that are easily recognised by the body (Grobler et al., 2008:285). The morphology and size of Pheroid™ is easily manipulated because it is a submicron emulsion type formulation which provides it with a vast flexibility profile (Grobler et al., 2008:284). Vesicular entrapment was used to entrap lidocaine HCl and prilocaine HCl in the Pheroid™ and incorporated into an emulgel formulation. An emulgel without the inclusion of Pheroid™ was formulated for comparison with the Pheroid™ emulgel as well as with a hydrogel. Pheroid™ solution was prepared and compared to a phosphate buffer solution (PBS) without Pheroid™, both containing lidocaine HCl and prilocaine HCl as APIs. Franz cell type transdermal diffusion studies were performed on the four semi-solid formulations (emulgel, Pheroid™ emulgel, hydrogel and the commercial product) and two solutions (PBS and Pheroid™). The diffusion studies were performed over a 12 h period followed by the tape stripping of the skin after each diffusion study. Caucasian female abdominal skin was obtained with consent from the donors. The skin for the diffusion cells were prepared by using a Zimmer Dermatome®. PBS (pH 7.4) was prepared as the receptor phase of the diffusion studies. The receptor phase was extracted at certain pre-determined time intervals and analysed with high performance liquid chromatography (HPLC) to determine the amount of API that had traversed the skin. Stratum corneum-epidermis samples and epidermis-dermis samples were prepared and left over night at 4 °C and analysed the next day with HPLC. This was done to determine the amount of API that accumulated in the epidermis-dermis and the amount of API that were left on the outer skin layers (stratum corneum-epidermis). The results from the Franz cell diffusion studies indicated that the emulgel formulation without Pheroid™ shortened the lag time of lidocaine HCl and that the emulgel formulated with Pheroid™ shortened the lag time of prilocaine HCl, when compared to the commercial product. Pheroid™ did not enhance the flux of lidocaine HCl and prilocaine HCl into the skin. The hydrogel formulation demonstrated a high transdermal flux of prilocaine HCl due to the hydrating effect it had on the stratum corneum. The commercial product yielded high flux values for both APIs but it did not result in a high concentration of the APIs delivered to the epidermis-dermis. Pheroid™ technology did, however, enhance the epidermal-dermal delivery of lidocaine HCl and prilocaine HCl into the skin epidermis-dermis. The stability of the emulgel formulation, Pheroid™ emulgel formulation and the hydrogel formulation was examined over a 6 month period. The formulations were stored at 25 °C/60% RH, 30 °C/60% RH and 40 °C/75% RH. The API concentration, mass, pH, zeta potential, particle size, viscosity and visual appearance for each formulation at the different storage conditions were noted and compared at month 0, 1, 2, 3 and 6 to determine if the formulations remained stable for 6 months. The results obtained from the stability study demonstrated that none of the formulations were stable for 6 months. The emulgel remained stable for the first 3 months. At 6 months, large decreases in API concentration and pH occurred which could cause a loss of anaesthetic action in the formulations. The Pheroid™ emulgel formulation did not remain stable for 6 months. / Thesis (MSc (Pharmaceutics))--North-West University, Potchefstroom Campus, 2013.