RESUMEN

BACKGROUND: Topical amitriptyline has been described as having mixed clinical efficacy for neuropathic pain. A few case reports using higher concentrations of this compound found clinical benefit, but many of these studies did not describe the components used in formulating the amitriptyline preparations. OBJECTIVE: To generate reproducible clinical measures of the characteristics of amitriptyline diffusion from selected compounding bases, to support a scientific approach to base selection when compounding this drug for neuropathic pain. METHODS: Amitriptyline hydrochloride (1%, 5%, and 10%) was compounded with 3 proprietary compounding bases: Lipoderm base, Emollient Cream, and Mediflo 30 pluronic lecithin organogel (PLO) gel. In vitro release of the drug from each base and subsequent permeation across artificial human skin were investigated with the Franz diffusion system. Amitriptyline release mechanisms were determined with kinetic models. How quickly and to what extent the drug leaves each base to diffuse through the skin were characterized by determining steady-state flux, cumulative permeation, and lag times. RESULTS: Release of amitriptyline was significantly higher from the Mediflo PLO gel than from the Lipoderm base or Emollient Cream (p < 0.05). Mean cumulative drug release after 24 h, from the 10% formulation, was 23.9% (standard deviation [SD] 4.1%) for Lipoderm base, 41.8% (SD 3.1%) for Emollient Cream, and 53.2% (SD 7.7%) for Mediflo PLO gel. A high percentage of amitriptyline was retained in all 3 bases. Although amitriptyline release was highest with Mediflo PLO gel, this base resulted in significantly lower cumulative permeation relative to Lipoderm base and Emollient Cream (p < 0.05). There was a strong overall correlation between amitriptyline concentration, lag time, and flux. Higher concentrations were associated with significantly lower lag times and increased flux. The highest lag time and flux were observed for Mediflo PLO gel. CONCLUSION: These data indicate that the therapeutic effectiveness of compounded amitriptyline for neuropathic pain depends on its diffusion out of the compounding bases and penetration through the skin.

CONTEXTE: L'efficacité clinique de l'amitriptyline topique contre les douleurs neuropathiques a été décrite comme étant variable. Quelques rapports utilisant des concentrations plus élevées de cette base indiquent des avantages cliniques, mais bon nombre d'entre eux ne décrivent pas les composants des préparations d'amitriptyline. OBJECTIF: Établir des mesures cliniques reproductibles des caractéristiques de la diffusion de l'amitriptyline selon une approche scientifique de la sélection des bases pour la préparation de ce médicament contre les douleurs neuropathiques. MÉTHODES: Le chlorohydrate d'amitriptyline (1 %, 5 % et 10 %) a été mélangé à trois bases de préparations magistrales brevetées : la base Lipoderm, la crème émolliente et le gel Mediflo PLO 30. La libération in vitro du médicament de chaque base et la perméation qui s'en est suivie dans la peau humaine artificielle ont été étudiées à l'aide du système de diffusion Franz. La définition des mécanismes de libération de l'amitriptyline repose sur des modèles cinétiques. La rapidité et la durée de libération du médicament de chaque base pour se diffuser dans la peau ont été caractérisées par la détermination du flux constant, de la perméation cumulée et des temps de latence. RÉSULTATS: La libération de l'amitriptyline était sensiblement plus élevée quand le produit était mélangé au gel Mediflo PLO plutôt qu'à la base Lipoderm ou à la crème émolliente (p < 0,05). La libération cumulée du médicament, formule 10 %, après 24 h était de 23,9 % (écart type [É.T.] ± 4,1 %) avec la base Lipoderm; 41,8 % (É.T. ± 3,1 %) avec la crème émolliente et 53,2 % (É.T. ± 7,7 %) avec le gel Mediflo PLO. Les trois bases retenaient un pourcentage élevé d'amitriptyline. Bien que la libération d'amitriptyline était plus élevée en présence du gel Mediflo PLO, la perméation cumulée de cette base par rapport à celle de la base Lipoderm et de la crème émolliente était sensiblement moins élevée (p < 0,05). L'observation a révélé une forte corrélation générale entre la concentration d'amitriptyline, le temps de latence et le flux. Les concentrations plus élevées étaient associées à des temps de latence sensiblement moins élevés. C'est le gel Mediflo PLO qui a démontré une supériorité du temps de latence et du flux. CONCLUSION: Ces données indiquent que l'efficacité thérapeutique de la préparation d'amitriptyline contre les douleurs neuropathiques dépend de sa diffusion hors des bases dans les préparations magistrales et de sa pénétration dans la peau.

RESUMEN

The objective of this study was to investigate the effect of Lipoderm Cream, VersaBase Gel, and Emollient Cream on the release and permeation of gabapentin formulated for neuropathic pain. Gabapentin of different strengths (1%, 5%, and 10%) was compounded with the bases, diffusion of the drug from thebases, and permeation through artificial skin model studied with Franz diffusionsystem. Steady-state flux, cumulative permeation, and lag times were calculated,and release mechanisms modelled with first order, second-order, Higuchi, Korsmeyer-Peppas, and Hixon-Crowell kinetic models. Gabapentin recovery from VersaBase Gel, Lipoderm Cream, and Emollient Cream was 100.8 ± 2.7%, 101.3 ± 1.2%, and 104.9 ± 3.3%, respectively. Gabapentin completely diffused out of the three bases within 6 hours of application according to the Higuchi model. Flux of the drug appeared to be concentration-dependent with no permeation occurring at 1% strength. Whereas, 5% and 10% strengths in Lipoderm Cream permeated the skin rapidly, the same concentrations in Emollient Cream and VersaBase Gel required 60-minutes and 120-minutes lag times, respectively. For the three bases, a strong correlation was observed between lag times and flux. The overall permeation in VersaBase Gel and Lipoderm Base was not significantly different (P>0.05). However, Emollient Cream resulted in a significantly lower total permeation compared to other bases (P<0.05). As the formulations are for pain management, products with no lag times and higher flux are preferable. Although VersaBase Gel and Emollient Cream displayed some gabapentin permeability, it is important to consider gabapentin stability in these bases prior to use.

Asunto(s)

RESUMEN

OBJECTIVES: To investigate the stability and beyond-use date (BUD) of topical gabapentin in 3 commonly used bases. METHODS: Lipoderm cream, Versabase gel, and Emollient cream were used to compound gabapentin (10%). The products were stored in Ecolojars, kept at 25°C, 4°C, and 40°C, and samples were collected on different days (days 0, 14, 28, and 90). Potency, stability, and organoleptic changes were monitored. RESULTS: At 25°C and 40°C, the potency of gabapentin in Lipoderm cream significantly increased (P < 0.05) after 28 and 90 days, respectively. In contrast, gabapentin degraded in Emollient cream (P < 0.05). At 25°C, the organoleptic properties of the drug compounded with Lipoderm cream (25°C) remained consistent for up to 28 days but showed signs of physical changes in other bases. Gabapentin recrystallized from Versabase gel and Emollient cream within 14 days. CONCLUSION: Gabapentin compounded with Lipoderm cream for topical use was stable in Ecolojars for 28 days at 25°C. Under the same conditions, the drug was not stable in Versabase gel and Emollient cream. Based on our stability and potency data, the beyond-use date of currently dispensed gabapentin (10%) formulations with Lipoderm cream should not be extended beyond the currently assigned 30-day mark, even when refrigerated. It is unclear whether the stability of these formulations is improved if stored in air-tight containers.

Asunto(s)

RESUMEN

Extemporaneous topical compounds for neuropathic pain offers an alternative or adjunct approach to existing therapies for patients. Assigning evidence-based beyond-use dating prior to dispensing topical medications is a legal requirement by pharmacy governing bodies. The purpose of this study was to utilize a validated stability-indicating high-performance liquid chromatography assay to determine beyond-use dating of topical amitriptyline in three different bases (Lipoderm Base, PLO Gel Mediflo 30, Emollient Cream) at three different temperatures [room temperature (25°C), refrigeration (4°C), and high temperature (40°C)]. Amitriptyline was stable after 90 days at room temperature in both Lipoderm Base and PLO Gel Mediflo 30. However, it was not stable at 40°C in Emollient Cream, irrespective of storage conditions.

Asunto(s)

RESUMEN

Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous airway diseases associated with significant morbidity and mortality. Pharmacological treatment is delivered primarily through the inhalation route using various devices. Optimal disease control is highly dependent upon patient adherence. Both patients with asthma and COPD are prone to exacerbations leading to hospitalization, which can significantly impact quality of life. Poor adherence is a complex and multifactorial problem that does not have one simple solution. However, it is the biggest risk factor for exacerbations and consequently high healthcare utilization. This review discusses the complex and multifactorial obstacles that impact patient adherence as well as the effect on overall treatment outcomes and healthcare utilization. We also critically examined and compared relatively recent improvements in breath-activated pressurized metered dose inhalers, dry powder inhalers, and e-technology in asthma and COPD. Finally, future treatment strategies for better patient compliance such as personalized medicine and the importance of decision-making between patients and physicians were highlighted.