Anderson de Oliveira Ferreira

Feasibility of amlodipine besylate, chloroquine phosphate, dapsone, phenytoin, pyridoxine hydrochloride, sulfadiazine, sulfasalazine, tetracycline hydrochloride, trimethoprim and zonisamide in SyrSpend® SF PH4 oral suspensions

The objective of this study was to evaluate the feasibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend(®) SF PH4 liquid): (i) amlodipine, (as besylate) 1.0mg/mL; (ii) chloroquine phosphate,15.0 mg/mL; (iii) dapsone, 2.0 mg/mL; (iv) phenytoin, 15.0 mg/mL; (v) pyridoxine hydrochloride, 50.0 mg/mL; (vi) sulfadiazine, 100.0 mg/mL; (vii) sulfasalazine, 100.0 mg/mL; (viii) tetracycline hydrochloride, 25.0 mg/mL; (ix) trimethoprim, 10.0 mg/mL; and (x) zonisamide, 10.0 mg/mL. All suspensions were stored both at controlled refrigeration (2-8 °C) and controlled room temperature (20-25 °C). Feasibility was assessed by measuring the percent recovery at varying time points throughout a 90-day period. API quantification was performed by high-performance liquid chromatography (HPLC-UV), via a stability-indicating method. Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was at least 90 days for all suspensions with regard to both the controlled temperatures. This suggests that the vehicle is stable for compounding APIs from different pharmacological classes.

Optimization of a new dissolution test for oxcarbazepine capsules using mixed-level factorial design

Neste trabalho foi desenvolvido e validado um teste de dissolucao para capsulas de oxcarbazepina. Para o estudo de triagem, foi utilizado um planejamento experimental de niveis mistos composto de fatores com dois e tres niveis (32 × 2), de modo a selecionar a velocidade de agitacao, o meio de dissolucao e o aparato. Esta estrategia e util, pois reduz o tempo de desenvolvimento do metodo e tambem gera resultados mais exatos. A melhor porcentagem de dissolucao foi obtida utilizando o aparato pa a 80 rpm e com solucao aquosa de laurilsulfato de sodio a 1% m/v como meio de dissolucao. A quantificacao da massa dissolvida foi realizada por analise espectrofotometrica UV-Vis a 304 nm. Os resultados do estudo da validacao demonstraram que o metodo e preciso e linear no intervalo de 83-249 µg mL-1 de oxcarbazepina. Os resultados evidenciaram que o metodo apresenta utilidade e adequabilidade para o estudo da dissolucao de capsulas de oxcarbazepina, uma vez que nao existe metodo oficial com este proposito.

Studies with Emulsion Containing trans-resveratrol: in vitro Release Profile and ex vivo Human Skin Permeation

Resveratrol is a phenolic compound that has been widely studied in the last years because of its extensive pharmacological properties. It also has physicochemical properties that are adequate for diffusion through the human skin. An analytical method by high performance liquid chromatography was developed and validated for its determination in transdermal emulsion, as well in receptor media and skin layers. The trans-resveratrol release kinetic followed the Higushis model (R(2) = 0.9926) with steady-state diffusion flux and lag time of 138.5 µg cm(-2) h(-1) and 0.49 h, respectively. It showed a percentage at 64.96 % for permeation. Thus, the results suggest that the emulsion studied is a potential vehicle for transresveratrol administration by transdermal route.

Delivering Resveratrol on the Buccal Mucosa Using Mucoadhesive Tablets: A Potential Treatment Strategy for Inflammatory Oral Lesions

BACKGROUND Resveratrol is a polyphenol that has gained momentum in therapeutics in the last few years. OBJECTIVE In this study, we hypothesised that resveratrol could act prophylactically and/or treat inflammatory lesions of the oral cavity after being delivered by two different formulations of buccal mucoadhesive tablets (F1 and F2, which differed in terms of viscosity agents used). METHODS This hypothesis was assessed through permeation studies, to verify diffusion of the drug through the buccal mucosa using a porcine model to predict human in vivo behaviour. RESULTS F2 (tablet with less viscosity agent) presented better permeation than F1, but the amount of drug that crossed the mucosa was still low compared to the amount retained within it (35.90 µg found in the receptor medium and 15.63 mg quantified within the mucosa). CONCLUSION This accounted for a local effect rather than a systemic one, which is desirable for local processes, such as oral mucositis, lichen planus, erythema multiforme, nicotinic stomatitis, recurrent aphthous stomatitis, among others. In this sense, resveratrol-loaded mucoadhesive tablets appear to be a prominent alternative to prevent and/or cure inflammatory lesions of the oral cavity.

Compatibility of caffeine, carvedilol, clomipramine hydrochloride, folic acid, hydrochlorothiazide, loperamide hydrochloride, methotrexate, nadolol, naltrexone hydrochloride and pentoxifylline in SyrSpend SF PH4 oral suspensions

Objectives The objective of this study was to evaluate the compatibility of 10 commonly used active pharmaceutical ingredients (APIs) compounded in oral suspensions using a globally available suspending vehicle (SyrSpend SF PH4 liquid): caffeine 10.0 mg/mL, carvedilol 1.0 mg/mL, clomipramine hydrochloride 5.0 mg/mL, folic acid 1.0 mg/mL, hydrochlorothiazide 5.0 mg/mL, loperamide hydrochloride 1.0 mg/mL, methotrexate 2.5 mg/mL, nadolol 10.0 mg/mL, naltrexone hydrochloride 1.0 mg/mL and pentoxifylline 20.0 mg/mL, stored at both controlled refrigerated (2–8°C) and room (20–25°C) temperature. Methods Compatibility was assessed by measuring the per cent recovery at different time points throughout a 90-day period. Quantification of the APIs was performed by high performance liquid chromatography (HPLC-UV) using a stability-indicating method. Results Methods were adequately validated. Forced degradation studies showed that at least one parameter influenced the stability of the APIs. All suspensions were assayed and showed API contents of between 90% and 110% over 90 days. Discussion Given the percentage of recovery of the APIs within the suspensions, the expiration date of the final products (API+vehicle) was found to be at least 90 days for all suspensions, for both controlled refrigerated and room temperature. Conclusions The results suggest that SyrSpend SF PH4 liquid is a stable suspending vehicle for compounding APIs from different pharmacological classes.

Green tea in transdermal formulation: HPLC method for quality control and in vitro drug release assays

RP-HPLC based analytical method for use in both quality control of green tea in a semisolid formulation and for in vitro drug release assays was developed and validated. The method was precise (CV 0.99), robust, and specific for the determination of epigallocatechin 3-gallate (EGCG), caffeine (CAF), and gallic acid (GA). In a diffusion cell chamber, the release rate of EGCG was 8896.01 µg cm-2. This data showed that EGCG will be able to exert its systemic activity when delivered though the transdermal formulation, due to its good flux rates with the synthetic membrane.

Compatibility of proton pump inhibitors in a preservative-free suspending vehicle

Objectives To evaluate the microbiological and physicochemical compatibility of commonly used proton pump inhibitors (PPIs) esomeprazole, lansoprazole, omeprazole and pantoprazole compounded at a single concentration using SyrSpend SF Alka and stored at refrigerated temperatures (omeprazole was also stored at room temperature because it has the most widespread use). Methods Compatibility was assessed by measuring the per cent recovery at varying time points throughout a 90-day period. Quantification of the APIs was performed by a validated high performance liquid chromatography (HPLC-UV) method. This same assay was also used to determine the dosage content uniformity of the suspensions. Microbiological stability (‘test in use’) was assessed during 60 days and total aerobic microbial count (TAMC), total combined yeasts and moulds count (TYMC), detection of Escherichia coli and pH determination were performed. Antimicrobial effectiveness testing was determined following European Pharmacopoeia guidelines. Results Beyond-use dates of maximum 60 days for omeprazole (5 mg/mL), pantoprazole (3 mg/mL) and esomeprazole (3 mg/mL) were established. All suspensions that met the physicochemical criteria for stability also met the content uniformity criteria. The suspensions showed no antimicrobial efficiency against bacteria, yeasts and moulds as SyrSpend SF Alka is an unpreserved vehicle, but the ‘test in use’ showed that the suspensions can remain microbiologically stable for up to 60 days. Conclusions SyrSpend SF Alka can be used to compound palatable (taste-masking properties) preservative-free oral suspensions with almost all commonly used PPIs.

Permeation Efficacy of a Transdermal Vehicle with Steroidal Hormones and Nonsteroidal Anti-inflammatory Agents as Model Drugs

BACKGROUND Transdermal delivery is an alternative route for the administration of drugs. However, it requires the development of vehicles that allow the drugs to cross the layers of the skin and reach the systemic circulation. OBJECTIVE In this study, a new transdermal vehicle was evaluated using progesterone, estradiol, estradiol + estriol (Biest) and ketoprofen administered as model drugs. METHODS To evaluate the ex vivo permeation of the drugs, the Franz vertical diffusion cell with human skin was used. RESULTS After 24 h, the vehicle was able to deliver 18.32 µg/cm2 of progesterone and 92.07 µg/cm2 of ketoprofen through the skin to the receptor medium. The permeation percentages were 91%, 78.8%, 48.5%, 73.2%, and 63.6%, respectively, for estradiol, estradiol (Biest), estriol (Biest), progesterone and ketoprofen. For all drugs, sufficient amounts were delivered to achieve a systemic effect, and it was also possible to decrease the amount of emulsion applied. CONCLUSION Thus, the vehicle demonstrated a high performance and the possibility of it being used for drugs that present difficulties in regards to administration by the transdermal route.

Taxifolin: Evaluation Through Ex vivo Permeations on Human Skin and Porcine Vaginal Mucosa

BACKGROUND Taxifolin (TAX) is a flavonoid that has numerous pharmacological properties, including an antioxidant ability superior to that of other flavonoids due to its particular structure. Nevertheless, it has low oral bioavailability, which limits its therapeutic application. In this context, potentially important approaches for systemic drug delivery could be by alternative routes such as skin and vaginal mucosa, once both routes have a variety of advantages compared with the oral route, including the ability to bypass both first-pass hepatic metabolism and the consequent degradation in the gastrointestinal tract. Vaginal delivery could also account for a local effect, or an effect on circumvent microregion. OBJECTIVE The major objective of this study was to develop and validate a high-performance liquid chromatography (HPLC) method for the determination of TAX in a semisolid dosage forms and then to evaluate ex vivo permeations across porcine vaginal mucosa and human skin. METHODS TAX was incorporated into an oil-in-water emulsion developed previously by our group. Method for quantification was developed and validated using HPLC. Permeation through human skin and vaginal porcine mucosa were conducted in Franz-type cells. RESULTS The method was precise (CV < 5%), accurate (recovery between 98% and 102%), linear (R2> 0.99), specific, and robust. Permeation experiments through porcine vaginal mucosa and human skin presented permeated percentages equal to 87.43% and 48.09% (per dose), respectively. CONCLUSION The results suggest that, in the matrixes studied, TAX may be able to exert its biological activities systemically when applied by these routes. Furthermore, it exhibits greater permeability potential when administered by intravaginal route.

Ex vivo Skin Permeation Evaluation of An Innovative Transdermal Vehicle Using Nimesulide and Piroxicam as Model Drugs

BACKGROUND The transdermal dosage forms presented a limited usage for a long time, for it was believed that the stratum corneum, the outermost layer of epidermis, made it impracticable the permeation of medications through the skin. Studies exploring this area came up with strategies to overcome this barrier; for example, creating a transdermal vehicle to facilitate the drug absorption. OBJECTIVE This study aimed to evaluate a new transdermal vehicle through the comparison of its permeation profile and the profile of commercial products, using nimesulide and piroxicam, non steroidal anti-inflammatory drugs. METHODS Four different products were evaluated: nimesulide and piroxicam compounded with the new vehicle (emulsion) and commercial nimesulide and piroxicam gels. Ex vivo permeation experiments using Franz-type diffusion cell equipment were conducted, using human skin as membrane. For evaluation of permeated active pharmaceutical ingredients concentrations, we performed quantification from the receptor solution, stratum corneum and viable epidermis + dermis, through high-performance liquid chromatography analyses. RESULTS The new vehicle promoted increased permeation of active pharmaceutical ingredients through the viable epidermis and dermis, when compared to commercial products, but the stratum corrneum continued to keep the highest retention. CONCLUSION The innovative vehicle was capable of enhancing the transdermal absorption of active pharmaceutical ingredients from the compounded formulations, thus, demonstrating the capability thereof to improve the permeability of active pharmaceutical ingredients by transdermal use.