Category: Formulation and Quality
Purpose: Pharmaceutical compounding is the art of creating customized medication products for patients who cannot use FDA-approved drugs. Allergy-free medications, alternative dosage forms and access to discontinued products are just of few of the advantages of this vital service. However complicated, multi-step preparations tend to be error-prone leading to inconsistency in potency, uniformity, and reproducibility (1-3). Lidocaine is a local anesthetic drug. Topical lidocaine gel relieves postherpetic neuralgia and also widely used during surgery (cataract, dental etc.) to manage pain because it is safe and highly effective (4,5). The objective of this study was to develop a single step compounding procedure for a carbomer 940 based 2% lidocaine gel (CLG) that’s more efficient and easier for both student-pharmacists and compounders to produce an elegant, error-free product.
Methods: The direct compounding procedure for CLG called for all formulation ingredients to be added directly into the dispensing container in a scientific manner followed by 2 minutes of mixing using an Unguator. To compound 30 g of CLG, a 50 ml dispensing container was placed on the scale and tared to zero. Then lidocaine (0.6g), propylene glycol (3g), and alcohol (9g) were weighed directly into the dispensing container and swirled gently for 1 minute to dissolve the drug. Next, carbomer 940 (0.15g) was added into the mix and swirled again for 1 minute to disperse the base. Finally, water was added q.s to 30 g and mixed for 2 minutes using the Unguator. The procedure was evaluated in terms of inter and intra examiner reliability and compared with the published data obtained by two different methods (%Assay ±SD: 115.5 ±7.2 & 94.6 ±20.5)6. Rheology, pH, permeability, %assay, and content uniformity of the LDG were also evaluated. To determine the content of lidocaine in LDG, the chromatographic separation was achieved with a Shimadzu Prominence HPLC system using isocratic elution mode on a Waters Xterra® MS C-18 column equipped with Ultraviolet-Visible (UV-Vis) Detector (220 nm). The release kinetics were evaluated using pig ear skin and Franz diffusion cells with a 9mm orifice diameter (Area: 0.64cm2) and 5ml receptor volume (95% Phosphate buffered saline and 5% of ethanol). Brookfield DV3T rheometer integrated with the helipath stand T-bar spindle was used to evaluate the viscosity of the CLG. The pH of CLG was determined by using both digital pH meter and pH test paper. Benchtop and accelerated (40ºC ± 2ºC/75% RH ± 5% RH) stability studies are in progress for two different formulations (with and w/o BHT) to evaluate the beyond use date and storage conditions.
Results: After optimization of the procedure and formulation, LDGs were compounded and characterized by the student-pharmacist and faculty. The study results indicate the newly developed user-friendly single-step formulation procedure produces a uniform, highly reproducible, and elegant (clear hydro-alcoholic gel) product with high yield (98.5%) in a short time (~ 10 minutes). The pH value of the CLG was found to be neutral (~7.0). This trouble-free procedure reduces inter and intra examiner product variation significantly in terms of content uniformity (%Assay ±SD; Intra:101.4% ±1.0, 101.9% ±1.7 & Inter: 101.7 % ±0.5) and viscosity (37500cP & 36830cP at 25°C). The viscosity of the lidocaine gel decreased as the shear rate (rpm) increased. This behavior is known as “shear-thinning (Non-Newtonian). The one-step compounding procedure also avoids cross-contamination with less mess to clean up. Representative HPLC chromatogram, rheological data, representation of compounding procedure and in vitro permeation profile are shown in figure 1.
Conclusion: The same procedure can be used for a similar class of drugs (in terms of physicochemical properties) to prepare other topical gels. Our findings suggest a straightforward, single step compounding procedure should be adopted by the pharmacy to compound Lidocaine Gel to improve both product quality and patient safety.