Analysis of spironolactone polymorphs in active pharmaceutical ingredients and their effect on tablet dissolution profiles

Abstract

Spironolactone (SPR) is a steroidal drug administered as a potassium-sparing diuretic for high blood pressure treatment. The drug shows incomplete gastrointestinal absorption due to its poor aqueous solubility. The physicochemical properties of SPR in crystal forms I and II suggest that differences in their aqueous solubility may lead to a lack of bioequivalence between solid-state formulations. In this study, SPR polymorphs in five batches of active pharmaceutical ingredients (APIs) from three manufacturers were characterized using powder X-ray diffraction, infrared spectroscopy, thermal analysis, and solubility measurements. SPR tablets (50 mg) were manufactured in our laboratory using API in pure form II, and API in form II contaminated with form I, which was found in a commercial batch. Physicochemical quality evaluations of the manufactured tablets, along with five SPR tablets marketed in Brazil, were performed, and results indicated differences in their dissolution profiles. In the manufactured tablets, differences were associated with the increased solubility of API in form II contaminated with form I compared to API in pure form II. In the marketed SPR tablets, the formulation composition demonstrated an important role in the dissolution rate of the drug, leading to lack of pharmaceutical equivalence among the drug products.Uniterms: Spironolactone/dissolution profile. Spironolactone/pharmaceutical equivalence. Spironolactone/solubility. Spironolactone/polymorphism. Drugs/quality assessment.

The Effect of Solvent Vapor Annealing on Drug-Loaded Electrospun Polymer Fibers

“…For SPL, characteristic peaks from thioacetyl and γ-lactone stretching appear at 1689 and 1764 cm −1 . Bands at 2867 and 2945 cm −1 correspond to symmetric and asymmetric CH2 stretching [30]. In the FT-IR spectrum of PCL-SPL-0 the characteristic peaks of both PCL and SPL are observed, confirming the presence of SPL in the fibers.…”

“…Given the hydrophobic nature of SPL (solubility in water: ca. 30 µg/mL −1 [30]), it is thought the residual must have adsorbed to the plasticware used during electrospinning.…”

The effect of polymorphism on active pharmaceutical ingredients: A review

“…Polymorphisms of pharmaceutical solids can modify the physicochemical properties when pharmaceutical solids exist in more than one crystal form or structure, signi icant differences in drug solubility can be detected, especially for drugs that are not soluble in water and are classi ied as class II and IV according to BCS (FDA, 2014;Bon ilio et al, 2014). In this case, the dissolution step is a limiting step for drug absorption, and the lack of bioequivalence between different formulations may be related to polymorphism (Resende et al, 2016).…”

“…Spironolactone (SPR) is a steroid drug given as a potassium-saving diuretic for high blood pressure treatment. According to the research of (Resende et al, 2016)solid-state formulations made with the same excipients and processes, the SPR polymorphism effect in drug solubilityand dissolution rate can change in vivo pharmacokinetics of this drug, which results in a lack of bioequivalence among medicinal products. The dissolution pro ile of tablets from batch A and B was shown where the amount of drug dissolved in 60 minutes was 89.32 ± 3.43% for batch A, and 79.55 ± 9.72% for batch B.…”

“…These results indicate a lack of pharmaceutical equality among the evaluated solid-state formulations. Therefore, formulation scientists must carefully explore the design of SPR formulations to optimize their performance and improve pharmaceutical equivalence and bioequivalence among drug products (Resende et al, 2016).…”