Development and Validation of a Discriminative Dissolution Test for Betamethasone Sodium Phosphate and Betamethasone Dipropionate Intramuscular Injectable Suspension

Abstract

Abstract. The intramuscular administration of the injectable suspension betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BD) has immediate therapeutic activity due to solubilized BSP and prolonged activity resulting from the slow release of BD micro-crystals. The purpose of this study was to develop and validate a dissolution method for BD in intramuscular injectable suspensions with detection by high-performance liquid chromatography (HPLC) method. Five commercial products presented a distribution of particle sizes, ranging between 7.43 and 40.25 μm as measured by laser diffraction. It was also found that particle sizes differed between batches of the same product. The different products were tested using the paddle apparatus, with stirring speeds of 25 and 50 rpm in 300 mL of phosphate buffer; simulated body fluid, muscle fluid, and synovial fluid were used as biorelevant dissolution media at 37±0.5°C. It was verified that not only does average particle size affect the dissolution rate, but also the mode and the polydispersity index of the particles. Discriminatory power was obtained using the in vitro dissolution method with 0.1 M sodium phosphate buffer pH 7.4 containing 0.1% sodium lauryl sulfate and a stirring speed of 50 rpm. The HPLC-method is linear, precise, selective, and accurate for the quantification of BSP and BD in dissolution profile testing. This dissolution method can be utilized as a method to control the quality of these injectable suspensions.KEY WORDS: dipropionate betamethasone; dissolution test; intramuscular injectable suspensions; simulated muscular fluid; sodium phosphate betamethasone.

Development of Betamethasone Dipropionate-Loaded Nanostructured Lipid Carriers for Topical and Transdermal Delivery

“…Dissolution medium was chosen to consist of phosphate buffer, pH 5.5, containing tween 80 (1% W/W) for enhancing betamethasone dipropionate solubility conserving sink conditions [21].…”

Human tissue-engineered skeletal muscle: a novel 3D in vitro model for drug disposition and toxicity after intramuscular injection

“…Due to lack of alternatives, candidate drugs and drug formulations for intramuscular administration are tested using methods developed for oral drug administration. In vitro dissolution testing of candidate drugs is used to predict in vivo drug release profiles 28 – 31 . But in vitro results obtained from these studies cannot adequately predict in vivo behavior of intramuscular drug formulations, due to a lack of good representation of the complex muscle physiology.…”

Dissolution-Controlled Salt of Pramipexole for Parenteral Administration: In Vitro Assessment and Mathematical Modeling

“…In this case, sink conditions are different than oral dosage forms, and the drug releases over a longer time period due to formation of depot at the site of injection. Therefore, a modified dissolution method was required to mimic the in vivo conditions (10). So, further dissolution studies were performed using a dialysis sac in USP apparatus 2 with 300 mL of dissolution media and a paddle speed of 25 rpm.…”

“…Apart from that, the in vitro dissolution study assists in product quality control by evaluation of batch-tobatch consistency at the early stages of the product development and facilitates regulatory approvals by assessment of scale-up and post-approval changes (SUPAC) (10,11).…”

“…Hence, there is a lack of a standardized, compendial in vitro method to simulate in vivo conditions for poorly water-soluble salts. Various regulatory bodies are highly interested in developing dissolution methods for parenteral suspension formulations (10).…”