Stability Indicating HPTLC Method for Simultaneous Determination of Amlodipine Besylate and Lisinopril in Combined Dose Tablet Formulation

A combined dose tablet formulation containing Amlodipine besylate and Lisinopril is used for the treatment of essential hypertension. The present study reports development and validation of stability indicating high performance thin layer chromatographic method for simultaneous estimation of these drugs in combined dose tablet formulation. The two drugs were satisfactorily resolved on aluminum plates precoated with silica gel 60F254 using n-butanol : methanol: ammonia (4:4:1 v/v/v) as mobile phase. The Rf value for lisinopril and amlodipine besylate were 0.27±0.02 and 0.62±0.02, respectively. Densitometric evaluation of the separated bands was performed at 215nm. The calibration curves for lisinopril and amlodipine besylate were found to be linear in the concentration range of 1000-6000ng/band. The method was validated as per ICH guidelines for accuracy, precision, robustness, specificity, limit of detection and limit of quantitation. Statistical analysis proves that the method is suitable for simultaneous analysis of Lisinopril and Amlodipine besylate in pharmaceutical formulation without any interference from the excipients/degradant. The developed method offers several advantages such as sensitive, rapid, cost effective and less time consuming as compared to the reported methods. As the method could effectively separate the drugs from its degradation products, it can be employed as a stability indicating method.

A Rare Disease of Familial Chylomicronemia Syndrome in a 20 Days Infant

Familial chylomicronemia syndrome is a group of very rare genetic disorders. It is inherited as autosomal recessive disorder. Its estimated incidence is 1 in 1000000 populations, characterized by deficient activity of an enzyme lipoprotein lipase (LPL) or apo-protein C-II, resulting into severe fasting hypertriglyceridemia and massive accumulations of chylomicrons in plasma. LPL deficiency typically presents in childhood with failure to thrive, colicky abdominal pain, eruptive xanthomas, lipemiaretinalis, pancreatitis and hepatomegaly. We are reporting a rare case of familial chylomicronemia in a 20 days old child who was presented with pneumonia, his plasma incidentally found like milk during routine collection of his blood sample. As the child was only 20 days old with very high triglyceride level, so breast feeding continued and cocktail therapy with low dose Tablet Fenofibrate, Tablet Niacin, Tablet Atovastatin started after referral to paediatric cardiologist at 3 months of age. Journal of Armed Forces Medical College Bangladesh Vol.15 (1) 2019: 107-109

The Comparison of Two Challenging Low Dose APIs in a Continuous Direct Compression Process

Segregation is a common problem in batch-based direct compression (BDC) processes, especially with low-dose tablet products, as is the preparation of a homogenous mixture. The scope of the current work was to explore if a continuous direct compression (CDC) process could serve as a solution for these challenges. Furthermore, the principle of a platform formulation was demonstrated for low dose tablets. The combination of filler excipients and the API in the formulation used was suitable for direct compression, but also prone to induce segregation in BDC process. The CDC process was found to be very promising; it was shown that tablets with the desired quality parameters could be manufactured successfully with both of the APIs studied. Powder analysis indicated that the APIs display some fundamental differences in their physical properties, which was also reflected in powder mixture properties and, hence, eventually in processing. However, process parameters, especially mixer impeller speed, were not found to have any significant influence on end product quality. The study suggests that a CDC process can be a viable solution to resolve the challenges described. Moreover, manufacturing by using a universal platform formulation seems to be a feasible way for producing low-dose tablets.

Linear pharmacokinetics of doxazosin in healthy subjects

Doxazosin is used for treating symptoms of benign prostatic hyperplasia (BPH). Besides, it is also prescribed for patients with mild to moderate essential hypertension. The object of the current study was to assess the linearity in the pharmacokinetics of doxazosin after administration of doxazosin as a single dose tablet containing 2, 4 and 8 mg doxazosin mesylate. Thirty Iraqi healthy male adult subjects were given 2, 4 and 8 mg doxazosin mesylate tablet in a randomized, cross-over, open-label, fasting, three-period, three-sequence design separated by one week wash out the interval between dosing. Serial blood samples were obtained from each subject before drug intake (zero time) and then at 0.33, 0.67, 1.0, 1.33, 1.67, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36, 48, 60, and eventually at 72 hours after dosing. The pharmacokinetic parameters Cmax, AUC0–t, AUC0–∞, Tmax and Thalf were determined from plasma concentration-time data of the drug by non-compartmental analysis. Statistical analysis of doxazosin pharmacokinetic parameters obtained after administration of the investigated dose ranges 2-8 mg demonstrated linear pharmacokinetics.

Homogenization of Amorphous Solid Dispersions Prepared by Electrospinning in Low-Dose Tablet Formulation

Low-dose tablet formulations were produced with excellent homogeneity based on drug-loaded electrospun fibers prepared by single-needle as well as scaled-up electrospinning (SNES and HSES). Carvedilol (CAR), a BCS II class compound, served as the model drug while poly (vinylpyrrolidone-co-vinyl acetate) (PVPVA64) was adopted as the fiber-forming polymer. Scanning electron microscopy (SEM) imaging was used to study the morphology of HSES and SNES samples. Different homogenization techniques were compared to maximize homogeneity: mixing in plastic bags and in a high-shear granulator resulting in low-shear mixing (LSM) and high-shear mixing (HSM). Drug content and homogeneity of the tablets were measured by UV-Vis spectrometry, the results revealed acceptably low-dose fluctuations especially with formulations homogenized with HSM. Sieve analysis was used on the final LSM and HSM powder mixtures in order to elucidate the observed differences between tablet homogeneity. Tablets containing drug-loaded electrospun fibers were also studied by Raman mapping demonstrating evenly distributed CAR within the corpus.