Academic literature on the topic 'Prilocaine HCl'

We have investigated two anesthetic agents, lidocaine hydrochloride (LD-HCl) and prilocaine hydrochloride (PRL-HCl), as well as their unionized counterparts, to explore the effect of intermolecular interactions on the formation and thermodynamic properties of eutectic mixtures.

The novel analytical method was developed and validated for determination of prilocaine HCl in bulk drug and pharmaceutical formulation by gas chromatography-nitrogen phosphorus detection (GC-NPD). The chromatographic separation was performed using a HP-5MS column. The calibration curve was linear over the concentration range of 40-1000 ng ml-1 with a correlation coefficient of 0.9998. The limits of detection (LOD) and quantification (LOQ) of method were 10 ng ml-1 and 35 ng ml-1, respectively. The within-day and between-day precision, expressed as the percent relative standard deviation (RSD%) was less than 5.0%, and accuracy (percent relative error) was better than 4.0%. The developed method can be directly and easily applied for determination of prilocaine HCl in bulk drug and pharmaceutical formulation using internal standard methodology.

SummaryTumescence local anaesthesia (TLA) is being increasingly used in varicose vein surgery. However, this requires doses of local anaesthetics that exceed the licensed limits. Whilst data exist for lidocaine and prilocaine, the literature rarely contains those for the local anaesthetic articaine. Patients, methods: Postoperative levels of methaemoglobin as well as plasma concentrations of articaine hydrochloride (articaine HCl) and articaine acid were measured in 100 patients who underwent varicose vein surgery under TLA after subcutaneous infiltration of 2.86 to 19.56 mg articaine pro kg body weight. With the first 20 patients, several blood samples for each parameter were collected at two-hour intervals to construct the plasma concentration versus time curves. In the following 80 patients, the plasma concentrations of methaemoglobin (MetHb), articaine HCl and articaine acid were each measured once only at the time of the previously determined average peak. Patient satisfaction, pre-, intra- and postoperative pain were recorded with the aid of questionnaires and the visual analogue scale (VAS). Results: Maximum concentrations of articaine HCl (n = 100) in plasma were 0.0034 to 0.5800 μg/ml (median: 0.0517 μg/ml) and were observed one hour after the start of infiltration. Values considered toxicologically harmful are >5 μg/ml. Levels of MetHb ranged from 0.19 to 1.90% (median: 0.78%) and were always normal. The median score on the VAS for the pain caused by TLA and the operation was 5 (0–10; n =4 3). Preoperative administration of 500 mg ibuprofen reduced the score to 3 (0–10; n = 40). Ibuprofen was well tolerated by the patients. Without ibuprofen, the patients were free of post-operative pain for 2 hours (0–10), while with ibuprofen, they were pain-free for 3.0 hours (0.5–9). Patient satisfaction was extremely high. 91.75% would agree to the same stripping operation being carried out in the same way again. Plasma concentrations of articaine acid, as the inert product of articaine HCl metabolism, peaked after 8 hours and were between 0.92 and 14.58 μg/ml (median: 3.95 μg/ml). Conclusion: The use of doses of up to 20 mg/kg body weight articaine in TLA appears to be a safe technique with high patient satisfaction. In comparison with prilocaine, the risk of methaemoglobinaemia is nil. Due to its structure, the use of articaine has none of the carcinogenic potential of the lidocaine metabolite, 2,6-dimethylalanine. The disadvantage of articaine is its rapid metabolism, which gives it a shorter duration of action and hence a shorter postoperative analgesia compared with prilocaine and lidocaine.

A 44-year-old female with paraesthesia and pain on the left anterolateral thigh who had been diagnosed with limb-girdle muscular dystrophy by electromyography and muscle biopsy is presented. Neurological examination revealed atrophy of the proximal muscles of both shoulders, plus pseudo hypertrophy of both calves. Electromyography exhibited a myopathic pattern. Musculoskeletal ultrasound imaging demonstrated a fusiform nerve swelling below the inguinal ligament suggesting lateral femoral cutaneous nerve compression, consistent with meralgia paraesthetica. Treatment with a perineural injection of betamethasone dipropionate and betamethasone sodium phosphate combination, and prilocaine-HCl, under ultrasound guidance, was performed. Symptoms resolved within 6 h. At 3-week follow-up, the patient was asymptomatic, and there was no paraesthesia or pain on examination. In this case, ultrasound-guided perineural injection of the lateral femoral cutaneous nerve with local anaesthetics and steroid served both diagnostic and therapeutic functions.

Background The aim of this study was to develop stable and easily injectable lipid depot preparations of local anesthetics in which the drug concentration can be varied according to desired duration of action. Methods The formulations contained a 2.0, 5.0, 10, 20, 40, 60, 80, or 100% eutectic mixture of lidocaine and prilocaine base in medium-chain triglyceride. Duration of sciatic nerve block and local neurotoxicity was investigated in rats with 2.0% lidocaine:prilocaine HCl solution and 99.5% ethanol as controls. The rate of release of local anesthetic from the site of administration and the possibility to predict in vivo depot characteristics from in vitro release data were investigated for the 20 and 60% formulations. Results The duration of sensory sciatic block was prolonged 3 times with the 20% formulation and approximately 180 times with the 60% formulation, in comparison with the 2% aqueous solution. With the 80 and 100% formulations, all animals still showed nerve block after 2 weeks. The in vivo release of local anesthetic could be approximately predicted from in vitro data for the 20% but not for the 60% formulation. The formulations of 60% or greater and ethanol showed neurotoxic effects. Conclusions The pharmaceutical properties of these formulations compare favorably with those of other depot preparations. The high-percentage ones showed the longest duration of action yet reported for sciatic nerve block in rats. The possibility of using a high-concentration local anesthetic depot formulation as an alternative to ethanol or phenol for long-term nerve blocks in chronic pain merits further investigation.

Abstract Objective : To compare the effectiveness of topically applied lidocaine-prilocaine cream with lidocaine-HCl injection in the reduction of pain during second degree of perineal tear suturing after vaginal delivery. Methods : One hundred and twenty-four of women with second degree of perineal tear after vaginal delivery were enrolled in this randomized clinical trial. Women were assigned randomly to have either application of lidocaine-prilocaine cream (n=62) or local injection of lidocaine-HCl (n=62) for anesthetic during perineal suturing. Pain measured with viasual analog scale (VAS) for the first 5 minutes during the perineal suturing. Statistical analysis was performed by comparative analytic numerical unpaired with independent t test between the two groups and significance was assessed at p<0.05. Data were presented as mean ± standard deviation (SD). Results : There was no significantly different of pain score between lidocaine-prilocaine cream and lidocaine-HCl injection group (5.66±1.07 vs 5.56±1.5; p=0.473). Conclusion : Application of lidocaine-prolicaine cream as effective as injection of lidocaine for reducing pain during second degree of perineal tear suturing after vaginal delivery. Keywords : Lidocaine-prilocaine cream, lidocaine-HCl injection, pain, perineal suturing, vaginal delivery Abstrak Tujuan: Untuk membandingkan efektivitas antara lidokain-prilokain topikal dan lidokain-HCl injeksi dalam mengurangi nyeri selama penjahitan luka perineum tingkat dua setelah persalinan normal. Metode: Seratus dua puluh empat perempuan dengan robekan perineum tingkat dua postpartum pervaginam mengikuti uji coba klinis secara acak ini. Enam puluh dua perempuan (n=62) menggunakan lidokain-prilokain topikal dan 62 perempuan lainnya (n=62) menggunakan injeksi lokal lidokain-HCl untuk anestesi selama penjahitan perineum. Nyeri diukur dengan visual analog scale (VAS) untuk 5 menit pertama selama penjahitan perineum. Analisis statistik dilakukan dengan uji numerik komparatif tidak berpasangan dengan uji t independen antara kedua kelompok dengan tingkat kemaknaan p<0,05. Data disajikan sebagai rerata ± standar deviasi (SD). Hasil: Tidak terdapat perbedaan signifikan skor nyeri antara kelompok lidokain-prilokain topikal dan kelompok injeksi lidokain-HCl (5,66 ± 1,07 vs 5,56 ± 1,5; p = 0,473). Kesimpulan : Efektifitas lidokain-prolikain topikal untuk mengurangi nyeri sama dengan injeksi lidokain-HCl selama penjahitan robekan perineum tingkat dua postpartum pervaginam. Kata kunci : Lidokain-prolikain topical, lidokain-HCl injeksi, nyeri, penjahitan perineum, persalinan normal

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.