Viscoelastic and Deformation Characteristics of Structurally Different Commercial Topical Systems

Rheological characteristics and shear response have potential implication in defining the pharmaceutical equivalence, therapeutic equivalence, and perceptive equivalence of commercial topical products. Three creams (C1 and C3 as oil-in-water and C2 as water-in-oil emulsions), and two gels (G1 and G2 carbomer-based) were characterized using the dynamic range of controlled shear in steady-state flow and oscillatory modes. All products, other than C3, met the Critical Quality Attribute criteria for high zero-shear viscosity (η0) of 2.6 × 104 to 1.5 × 105 Pa∙s and yield stress (τ0) of 55 to 277 Pa. C3 exhibited a smaller linear viscoelastic region and lower η0 (2547 Pa∙s) and τ0 (2 Pa), consistent with lotion-like behavior. All dose forms showed viscoelastic solid behavior having a storage modulus (G′) higher than the loss modulus (G″) in the linear viscoelastic region. However, the transition of G′ > G″ to G″ > G′ during the continual strain increment was more rapid for the creams, elucidating a relatively brittle deformation, whereas these transitions in gels were more prolonged, consistent with a gradual disentanglement of the polymer network. In conclusion, these analyses not only ensure quality and stability, but also enable the microstructure to be characterized as being flexible (gels) or inelastic (creams).

The Implications of Regulatory Framework for Topical Semisolid Drug Products: From Critical Quality and Performance Attributes towards Establishing Bioequivalence

Due to complex interdependent relationships affecting their microstructure, topical semisolid drug formulations face unique obstacles to the development of generics compared to other drug products. Traditionally, establishing bioequivalence is based on comparative clinical trials, which are expensive and often associated with high degrees of variability and low sensitivity in detecting formulation differences. To address this issue, leading regulatory agencies have aimed to advance guidelines relevant to topical generics, ultimately accepting different non-clinical, in vitro/in vivo surrogate methods for topical bioequivalence assessment. Unfortunately, according to both industry and academia stakeholders, these efforts are far from flawless, and often upsurge the potential for result variability and a number of other failure modes. This paper offers a comprehensive review of the literature focused on amending regulatory positions concerning the demonstration of (i) extended pharmaceutical equivalence and (ii) equivalence with respect to the efficacy of topical semisolids. The proposed corrective measures are disclosed and critically discussed, as they span from mere demands to widen the acceptance range (e.g., from ±10% to ±20%/±25% for rheology and in vitro release parameters highly prone to batch-to-batch variability) or reassess the optimal number of samples required to reach the desired statistical power, but also rely on specific data modeling or novel statistical approaches.

Assessment of the pharmaceutical equivalence and in vitro dissolution studies of amlodipine tablets marketed in Northern Nigeria

The extensive supply of poor quality and/or counterfeit drug products in many developing countries has made it vital to frequently carry out suitable tests to assess bioequivalence (BE) in a cost-effective manner. This study was intended to assess the pharmaceutical equivalence and dissolution profile of amlodipine 5mg tablets marketed in Jos and Kaduna metropolis. Ten brands of Amlodipine 5mg tablets were obtained from different community pharmacies and evaluated for different quality control parameters such as percent drug content, friability, hardness, thickness, weight uniformity, disintegration time, and dissolution. The results showed that brands F and I failed the test for percent drug content while the rest of the brands passed it. In addition, all the brands passed the disintegrationand friability test while Brands C, F and I did not pass the hardness test. The dissolution profiles of all the brands were similar to the innovator brand at pH 6.8, whereas at pH 1.2, only four brands (B, E, H and I) had similar dissolution profile to the innovator. This study serves to justify for the assessment of in vitro parameters of commercially available amlodipine generics which may aid the prescribers’ decision making. Keywords: Amlodipine; Jos; Tablet properties, Dissolution profile

Application of microbiological assay to determine the potency of intravenous antibiotics

Demonstration of equivalent amounts of active pharmaceutical ingredient is a basic requirement for intravenous generic drugs prior to administration. Physicochemical methods are often used to determine concentration of antibiotics in biological fluids. However, it does not permit direct quantification of potency of a desired antibiotic. This study demonstrates the application of a microbiological assay to determine the potency and concentration of commercially available pharmaceutical-grade antibiotics used for injections. Concentration-dependent variation of inhibitory effect of four commercial brands of cefuroxime and two of ciprofloxacin were observed against two reference bacteria (Escherichia coli DH5α and Escherichia coli ATCC 8739) on Mueller Hinton agar. Regression analysis was used to assess the in vitro equivalence of generic products sold by different retail companies in Dhaka city. A linear relationship was found between the concentration and response of the bacteria in regression analysis where anti-log of X-intercept and slope showed the concentration and potency, respectively. The study showed excellent results of linearity (r2≥0.89), precision (inter assay variation ≤10% for cefuroxime and ≤20% for ciprofloxacin), accuracy and specificity tests for both types of antibiotics. Pharmaceutical equivalence demonstrated by four cefuroxime and two ciprofloxacin samples showed no significantly distinguishable slopes (P > 0.78 and P > 0.44) and intercepts (P > 0.25 and P > 0.07), respectively. Estimated potency for cefuroxime was 91.1-100.0% and for ciprofloxacin was 68.1-100.0%. Microbiological assay was found to be convenient, rapid, cost-effective, precise and accurate in demonstrating pharmaceutical equivalence of antibiotics in different dosage forms. This technique can be used as an alternative method for testing generic antibiotics prior to their use in animal and human. Stamford Journal of Microbiology, Vol.10 (1) 2020: 25-29