In vitro Comparative Dissolution Studies of Different Propranolol Generic Tablets Available in Bangladesh

The present study focused to assess in vitro dissolution profiles of four different products of propranolol 10 mg Tablets (Randomly coded as PRP1-PRP4) available in Bangladesh comparing with the reference brand (coded as REF). Propranolol is a competitive non selective beta-adrenergic receptor antagonist used to amend or restore normal heart rhythm in cardiovascular diseases. An in vitro dissolution study was carried out using the United States Pharmacopoeia (USP) paddle method at 75 rpm with 500 mL of 0.1N HCl dissolution media at 37.0± 0.5 0C. All the tested locally manufactured propranolol products; PRP1, PRP2, PRP3, PRP4 showed compatible dissolution (87%, 86%, 87%, and 80%, respectively) pattern (dissolution criterion Q=80% in 30 minutes) compared with the reference brand (88% dissolution in 30 minutes). The dissolution behavior was estimated with the reference brand using a model dependent and model-independent approach (f2>50, f1 < 15). A mechanistic mathematical release kinetics was also evaluated. The best-fit kinetic model was Hixon-Crowell release kinetics for reference brand and PRP1; and first order release kinetics was predominant for PRP2, PRP3 and PRP4. Keywords: propranolol, dissolution, similarity factor, difference factor, dissolution kinetics

An Internal Standard High-Performance Liquid Chromatography Method for Simultaneous Quantification of Candesartan and Hydrochlorothiazide in Combined Formulations

The internal standard method is a versatile procedure that avoids misleading results caused by the instability of the chromatographic system or inexperienced workers. It is an effective way to judge the accuracy of any obtained data. As the detector responses of chlorzoxazone (CZN) resemble those of candesartan (CDZN) and hydrochlorothiazide (HCTZ), CZN was employed as an internal standard. Herein, a simple chromatographic method was established for quantification of CDZN and HCTZ. Isocratic elution was conducted using 1% premixed acetonitrile/formic acid (7:3 v/v) at a 0.8 mL/min flowrate. The separation of the three components was maintained using the universal 20 µL loop, and for further simplicity in application, the analysis was optimized at 25 °C. CDZN, HCTZ, and CZN were simultaneously monitored and quantified at 270 nm. The method developed here complies with all the validation limits according to the British Pharmacopoeia (BP), United States Pharmacopoeia (USP), and the guidelines of the International Council ForHarmonisation (ICH). The method proved to be linear in the range of 6.4 to 25.6 µg/mL and 5.0–20 µg/mL for CDZN and HCTZ, respectively, while the quantitation detection limits were less than 1.0µg/mL for both.

Shape fidelity and sterility assessment of 3D printed polycaprolactone and hydroxyapatite scaffolds

Polycaprolactone (PCL) and hydroxyapatite (HA) composite are widely used in tissue engineering (TE). They are fit to being processed with three-dimensional (3D) printing technique to create scaffolds with verifiable porosity. The current challenge is to guarantee the reliability and reproducibility of 3D printed scaffolds and to create sterile scaffolds which can be used for in vitro cell cultures. In this context it is important for successful cell culture, to have a protocol in order to evaluate the sterility of the printed scaffolds. We proposed a systematic approach to sterilise 90%PCL-10%HA pellets using a 3D bioprinter before starting the printing process. We evaluated the printability of PCL-HA composite and the shape fidelity of scaffolds printed with and without sterilised pellets varying infill pattern, and the sterility of 3D printed scaffolds following the method established by the United States Pharmacopoeia. Finally, the thermal analyses supported by the Fourier Transform Infrared Spectroscopy were useful to verify the stability of the sterilisation process in the PCL solid state with and without HA. The results show that the use of the 3D printer, according to the proposed protocol, allows to obtain sterile 3D PCL-HA scaffolds suitable for TE applications such as bone or cartilage repair.

Beyond-Use Dates Assignment for Pharmaceutical Preparations: Example of Low-Dose Amiodarone Capsules

Background: Beyond-use dates (BUDs) in compounding practice are assigned from stability studies. The United States Pharmacopoeia (USP 42 NF 37) suggested to assign a 6 months BUD for dry oral forms. A new pediatric formula of amiodarone capsules was implemented in our hospital, with 3 dosages (5 mg, 20 mg, and 50 mg). Objective: BUD of these new formulas had to be determined by stability study. Methods: The method for the determination of amiodarone content was validated to be stability indicating, and a stability study was performed. Different excipients commonly used for capsule compounding were compared. Results: We found that, with microcrystalline cellulose as excipient, 50 mg amiodarone capsules were stable for 1 year, whereas 5 mg and 20 mg capsules were not. This difference was studied, and lactose or mannitol were found to be better excipients for 5 mg amiodarone capsules, despite their potential side effects. A potential drug-excipient interaction between microcrystalline cellulose and amiodarone hydrochloride is described. Conclusion: Amiodarone hydrochloride/microcrystalline cellulose capsules have a BUD of 1 month for 5 mg capsules, 6 months for 20 mg, and 1 year for 50 mg.

Quality of Different Brands of Metronidazole Benzoate Oral Suspensions Available at Jimma Town, Southwest Ethiopia: Pharmaceuticals Quality Study

Background: Poor quality drugs include substandard and counterfeit medicines. Poor quality antibiotics selectively kill the susceptible strain and leaves resistant strain to multiply. Metronidazole is a broad spectrum antibiotic whose effectiveness depends up on a dose administered to the patient. Objective: The aim of the study is to assess the quality of different brands of metronidazole Benzoate oral suspension available in Jimma town, West Ethiopia. Methods: Cross-sectional study was conducted in Jimma town, West Ethiopia from Feb 08 – Mar 28, 2018. The assay result of all the seven brands of Metronidazole Benzoate oral suspensions was entered to statistical package for social sciences software version 24.0 for windows. Then, one way analysis of variance was performed using Tukey test to determine whether there exists significant difference in assay result of the brands (p<0.05). Result: All the seven Metronidazole benzoate oral suspensions assessed in this study passed British Pharmacopoeia 2013 specification of identity test of the drug. All the brands passed the assay test and total aerobic microbial count specification United States Pharmacopoeia 2015. The highest percentage of drug content was obtained for Metrolag, 105.56%, while the least content for Mizel, 93.12%. However, statistical comparison of drug contents at 95% confidence interval indicates that there is significant difference in drug content within and among the seven brands of Metronidazole benzoate oral suspensions (p<0.05). The pH of all the brands was with in United States Pharmacopoeia 2015 specification limit.

Evaluation of the Binding Properties of a Polymer Obtained from Modification of Triticum aestivum Starch in Metronidazole Tablets Formulation

Aim: The binding properties of a polymer obtained from modification of Triticum aestivum (TA) starch in metronidazole tablets formulation were evaluated. Study Design: Experimental design. Place and Duration of Study: Department of Pharmaceutics and Pharmaceutical Technology, University of Port Harcourt, Choba, Rivers State, Nigeria from January to July, 2018. Methods: TA seeds were steeped for 72 h, wet milled and the native Triticum aestivum starch (NTS) extracted. NTS (1kg) was oxidized by slurring in 4 L of 3.50% w/v sodium hypochlorite, washed to neutral pH with 95% v/v ethanol (MTS). MTS was dried at 60°C for 3 h, milled and classified (250 μm). The starches were characterized using standard methods and applied as binders at 1, 2 and 3% w/w in formulating metronidazole tablets using wet granulation. Methylcellulose and gelatin at similar concentrations were used as standards. Results: The granules and tablets were evaluated using standard methods. NTS and MTS had similar properties with starch. The modification improved the densities, hydration capacity and flow properties of MTS. The granules flowed and compressed well. The tablets had minimal weight variation, hardness (≥ 4 kgF), friability (<1%) and disintegration (<15 min). Metronidazole release (≥ 85%) within 60 min existed in all the batches except batches containing 1% methylcellulose and 3% gelatine. Conclusion: The results met with United States Pharmacopoeia specifications for oral uncoated metronidazole tablets. MTS performed better than NTS and compared well with methylcellulose and gelatin as binder in metronidazole tablet formulation.

Pharmaceutical quality of seven brands of diclofenac tablet on the Saudi market

Objective We previously reported the pharmaceutical quality of eight brands of 50 mg enteric-coated diclofenac sodium tablet available on the Saudi market. Here, we assess the quality of reference (R1) and four generic (G1–G4) brands of 50 mg immediate-release diclofenac potassium tablet and of reference (R2) and generic (G5) brands of 100 mg sustained-release diclofenac sodium tablet. Results Weight variation (range as % difference from mean), active substance content (mean (SD) as % difference from label), breaking force [mean (SD)], and friability (as % weight loss) were 95–104% and 99–102%, 100.9% (3.4%) and 105.6 (4.2%), 12.2 (1.3) and 12.9 (1.8) kg, and 0.0014% and 0.0012%, for R1 and R2, respectively. For G1-G5, they were ≤ ± 2%, 98.8% (2.7%) to 109.2% (3.8%), 6.4 (0.6) to 13.3 (1.0) kg, and 0.0007% to 0.0261%, respectively. R1 and G1-G4 disintegrated within 04:50–17:20 min: seconds and released a mean of 89–100% of label active substance content by 60 min in buffer (pH 6.8). R2 and G5 did not disintegrate or dissolve in 0.1 N HCl for 2 h, disintegrated in buffer (pH 6.8) in 01:58–02:15 h: minutes, and fulfilled dissolution criteria (pH 7.5) for both United States Pharmacopoeia test-1 and test-2. Thus all seven brands met pre-specified quality criteria.

Effectiveness of a Novel Dentifrice Containing Stabilized Chlorine Dioxide, Sarkosyl, and Sodium Fluoride

This in vitro study evaluated the effectiveness of a novel dentifrice containing stabilized chlorine dioxide, sodium lauroyl sarcosinate (sarkosyl), and sodium fluoride in enhancing enamel fluoride uptake, remineralization, pellicle cleaning and inhibiting biofilm regrowth. Remineralization was measured by fluoride uptake and surface microhardness assessment tests. Artificial stains were removed and scored based on pellicle cleaning ratio. Biofilm regrowth was measured by counting colonies on the agar plates. All studies were conducted using bovine teeth specimens. The efficacy of Toothpaste C (CloSYS anticavity toothpaste) was compared with United States Pharmacopoeia Reference Dentifrice, Toothpaste B (discontinued CloSYS anticavity toothpaste formulation) and leading commercial toothpastes. The enamel fluoride uptake and remineralization by Toothpaste C was 96.1% to 303.3% and 38.0% to 102.4% higher than the tested toothpastes, respectively. The mean pellicle cleaning ratio of Toothpaste C was similar to American Dental Association Reference Material. Toothpaste C had a significant reduction in regrowth of the oral polymicrobial biofilm compared to the control. All tested toothpastes contained 0.24% sodium fluoride. Toothpaste C exhibited significantly superior performance towards fluoride uptake and remineralization compared to the tested toothpastes. Therefore, toothpaste ingredients other than sodium fluoride accounted for the enhanced fluoride uptake and remineralization.

Eight enteric-coated 50 mg diclofenac sodium tablet formulations marketed in Saudi Arabia: in vitro quality evaluation

Objective To evaluate in vitro quality of enteric-coated 50 mg diclofenac sodium tablet formulations on Saudi market. Results A reference and seven generic (G1-7) formulations were commercially available in December 2019/January 2020 and were assessed within 25–75% of manufacture-expiration period. Weight variation (range as% difference from mean, n = 20), active substance content (ASC, mean (SD) as% difference from label, n = 20), hardness (mean (SD), n = 10), and friability (% weight loss, n = 20) were 97–103%, 102.0% (3.4%), 15.4 (1.1) kg, and 0.24%, respectively, for the reference. For G2-7, they were ≤ ±5%, 98.6% (4.0%) to 109.9% (1.8%), 11.9 (0.9) to 18.3 (0.8) kg, and ≤ 0.00 to 0.75%, respectively. G1 ASC, hardness, and friability were 111.3% (1.7%), 20.1 (1.7) kg, and 1.10%, respectively. Disintegration time (n = 6) and dissolution profile (n = 8) were also determined. No formulation disintegrated or released ˃ 0.1% of label ASC in 0.1 N HCl for 2 h. The reference disintegrated in 15:00 min:seconds and released a mean (range) of 100% (99–103%) of label ASC by 45 min in phosphate buffer (pH = 6.8). G1-7 disintegrated in 8:53 to 20:37 min:seconds and released 81% (69–90%) (G1) to 109%. Except for borderline performance of G1, all formulations passed in vitro quality tests according to United States Pharmacopoeia.