Pharmaceutical Capsules Research Articles

Garlic Peel-based Carbon Quantum Dots as a Sustainable Alternative for the Sensitive and Green Spectrofluorometric Quantification of Molnupiravir in Pharmaceutical Capsules

Searching for natural alternatives to replace environmentally harmful chemical reagents in analysis is just as crucial as finding easily accessible analytical tools. To reinforce these concepts, this study proposes a simple spectrofluorometric approach using natural carbon quantum dots (n-CQDs) as fluorescence probes for sensitive and environmentally friendly measurement of molnupiravir, an antiviral drug that was initially developed for influenza and has demonstrated potential efficacy against COVID-19. n-CQDs were synthesized using garlic peels (GP), a waste material, via a microwave-assisted method. n-CQDs have a characteristic broad absorbance and narrow emission spectrum, making it easier to analyze several targets. The GP-based n-CQDs showed maximum excitation/emission at 265/347 nm with an acceptable quantum yield. After reaction with molnupiravir, the produced n-CQDs demonstrated unique features to determine the tested analyte. Different factors influencing the synthesis of n-CQDs and their interaction with the studied drug, molnupiravir, were investigated and optimized. Using GP-based n-QCDs as fluorescent probe for measuring molnupiravir by FL, a green analytical approach based on the probes' fluorescence quenching was developed (GP- n-CQDs -QN-FL). The method demonstrated good linearity from 0.5 to 30 μg/mL and detection/quantitation limits of 0.19/0.5 μg/mL. Validation studies confirmed accuracy (98-102% recovery), precision (<2% RSD), robustness and selectivity. Various assessment indexes have been utilized to assess the environmental friendliness and suitability aspects of the suggested approach in comparison to other existing techniques. Furthermore, n-CQDs were successfully employed for the precise analysis of molnupiravir in its pharmaceutical capsules. The comprehensive results proved that the method can be deemed eco-friendly and feasible more than the other techniques for its intended purpose for molnupiravir determination in pharmaceutical dosage forms with an average recovery 101.17%.

Spectrophotometric determination of olanzapine, fluoxetine HCL and its impurity using univariate and chemometrics methods reinforced by latin hypercube sampling: Validation and eco-friendliness assessments

Novel univariate and chemometrics-aided UV spectrophotometric methods were tailored to undergo the fundamentals of green and white analytical chemistry for the simultaneous estimation of a ternary mixture of olanzapine (OLA), fluoxetine HCL (FLU), and its toxic impurity 4-(Trifluoromethyl) phenol (FMP) without any prior separation. The dual-wavelength ratio spectrum univariate method was used to determine OLA and FLU in the presence of FMP in the range of (4–20) and (5–50) μg/ml, respectively. In compliance with the International Conference on Harmonization (ICH) standards, the technique was validated and established Remarkable accuracy (98–102%) and precision (< 2%) with limits of quantification (LOQs) of 0.432 and 2.002 μg/ml, respectively. Partial least squares (PLS) and artificial neural networks (ANNs) are chemometric methodologies that have advantages over the univariate method and use significant innovations employing Latin hypercube sampling (LHS), allowing the generation of a reliable validation set to guarantee the effectiveness and sustainability of these models. The concentration ranges used were (2–20), (2–20), and (5–50) μg/ml; for PLS, the LOQs were 0.602, 0.508, and 1.429 μg/ml, and the root mean square errors of prediction (RMSEPs) were 0.087, 0.048, and 0.159 for OLA, FMP, and FLU, respectively; and for ANNs, the LOQs were 0.551, 0.465, and 0.965 μg/ml, with RMSEPs of 0.056, 0.047, and 0.087 for OLA, FMP, and FLU, respectively. The developed methods yield a greener National Environmental Methods Index (NEMI) with an eco-scale assessment (ESA) score of 90 and a complementary Green Analytical Procedure Index (complex GAPI) in quadrants with an analytical greenness metric (AGREE) score of 0.8. The Red‒Green–Blue 12 algorithm (RGB 12) scored 88.9, outperforming on reported methods and demonstrating widespread practical and environmental approval. Statistical analysis revealed no noteworthy differences (P > 0.05) among the proposed and published techniques. Both pure powders and pharmaceutical capsules were analyzed via these methods.

Eco-friendly second derivative synchronous fluorescence spectroscopic method for simultaneous determination of rosuvastatin and ezetimibe in pharmaceutical capsules

The fixed dose combination of Rosuvastatin and ezetimibe has recently received approval from the FDA for the treatment of elevated levels of low-density lipoprotein cholesterol in adults. Herein, an eco-friendly and highly sensitive spectrofluorimetric method was developed and validated for simultaneous determination of rosuvastatin and ezetimibe in commercial capsules. The developed method involved synchronous fluorescence spectroscopy combined with second derivative spectroscopy to resolve the overlapping fluorescence spectra of rosuvastatin and ezetimibe. The studied drugs were measured in synchronous mode at Δλ of 40 and their recorded synchronous fluorescence spectra were derivatized into second-order spectra, enabling the selective quantification of rosuvastatin and ezetimibe at 370 nm and 312 nm, respectively. Optimization studies regarding to the influence of buffer pH, incorporation of surfactant, choice of diluting solvent, and synchronous Δλ were carried out. The method was validated using the validation characteristics listed in ICH Q2(R1). The calibration curves displayed satisfactory linear relationships across the calibration range of 0.1–2 µg/mL for rosuvastatin and 0.05–3 µg/mL for ezetimibe. The methodology demonstrated robustness to minor modifications in the procedural parameters and selectivity in quantifying the studied drugs in synthetic mixed solutions and commercial capsules without interference. Furthermore, the level of environmental friendliness and sustainability of the suggested spectrofluorimetric approach was assessed in relation to two previously documented methodologies utilizing the AGREE metric. The findings indicated that the suggested method demonstrated a notably superior level of sustainability in comparison to the documented methods.

Highly sensitive electrochemical sensor for glutathione detection using zinc oxide quantum dots anchored on reduced graphene oxide

This work presents a highly sensitive and selective electrochemical sensor for glutathione (GSH) detection using a glassy carbon (GC) electrode modified with zinc oxide quantum dots-reduced graphene oxide nanocomposites (ZnO QDs-rGO NCs). The ZnO QDs (diameters about ∼2 to 8 nm) were synthesized and successfully anchored onto the surface of reduced graphene oxide (rGO). The resulting nanocomposites were then characterized using various spectroscopic and microscopic techniques. The wurtzite crystal structure of ZnO and anchored onto the rGO surface were confirmed by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The synergistic interaction between ZnO QDs with rGO provides a large surface area, high conductivity, and efficient transfer of electrons, resulting in improved electrocatalytic activity for GSH oxidation. The ZnO QDs-rGO/GC electrode exhibits exceptional performance with a wide linear range (0.01–10 μM), high sensitivity (3.66 μAμM−1), and excellent selectivity for GSH. The sensor demonstrates good analytical stability, characterized by high reproducibility (%RSD = 2.90%) and repeatability (%RSD = 1.49%), and maintains its performance in the presence of common biological interferences. The applicability of the sensor was validated through successful GSH detection in complex matrices like human blood and pharmaceutical capsules, achieving recovery rates of 98.1-102.0% with excellent reliability.

Development of a fluorescent nano-sensing probe for atomoxetine analysis: Additional clinical pharmacokinetic study

Atomoxetine is a psychostimulant drug used for the treatment of attention-deficit/hyperactivity disorder (ADHD) symptoms in people with autism. Herein, eco-friendly fluorescent carbon quantum dots (CQDs) were synthesized using black-eyed pea beans and characterized for the purpose of quantifying atomoxetine in pharmaceutical capsules and human plasma. The selectivity of these CQDs towards atomoxetine was improved by functionalizing their surface with an atomoxetine-tetraphenylborate ion complex. The quantification of atomoxetine is based on measuring the fluorescence quenching of the functionalized CQDs in response to varying concentrations of atomoxetine. The Stern-Volmer plot was employed to investigate the mechanism through which atomoxetine quenches the fluorescence intensity of the CQDs. The outcomes indicated a dynamic quenching mechanism. The applied method was optimized and validated in compliance with ICH requirements, resulting in excellent linearity across the concentration range of 50–800 ng/mL. The developed method was successfully used to quantify atomoxetine in pharmaceutical dosage form and human plasma with acceptable accuracy and precision outcomes. In addition, the method was applied for clinical pharmacokinetic study of atomoxetine in the plasma of children diagnosed with both autism and ADHD. Atomoxetine was rapidly absorbed after a single oral dose of 10 mg, reaching maximum concentration within two hours and having a half-life (t1/2) of 3.11 h. Moreover, the method demonstrates a notable degree of eco-friendliness, as evidenced by two greenness evaluation metrics; Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE).

Development of fluorescence probe for spectrofluorimetric determination of viloxazine hydrochloride in pharmaceutical form and rat plasma; additional pharmacokinetic study.

Attention deficit hyperactivity disorder (ADHD) is a neurological condition frequently identified in early childhood and frequently co-occurs with other neuropsychological disorders, particularly autism. Viloxazine hydrochloride, a non-stimulant medication, has recently gained approval for treating attention-deficit hyperactivity disorder. This paper describes the first spectrofluorimetric method for precisely measuring the content of viloxazine in pharmaceutical capsules and rat plasma. This method employed NBD-Cl (4-chloro-7-nitrobenzo-2-oxa-1,3-diazole) as a fluorescent probe, which transformed viloxazine in an alkaline environment into a remarkably sensitive fluorescent adduct. Upon excitation at 476 nm, this adduct becomes detectable at a wavelength of 536 nm. The method was validated using ICH criteria, revealing acceptable linearity across a concentration range of 200-2000 ng/ml and high sensitivity with LOD and LOQ values of 46.774 ng/ml and 141.741 ng/ml, respectively. This method was adeptly applied in a pharmacokinetic study of viloxazine in rat plasma following a single oral dose (10mg/kg), yielding a mean peak plasma concentration (Cmax) of 1721 ng/ml, achieved within 1.5h. Furthermore, the environmental impact of the technique was assessed using two greenness assessment tools, revealing a notable level of eco-friendliness and sustainability.

Dual benefits of NBD-Cl fluorogenic action and sample pretreatment (SALLE) technology in the assessment of anticoagulant medication: Dabigatran in pharmaceutical capsules and plasma samples.

Dabigatran (DBG), marketed as Pradaxa, is an anticoagulant medication prescribed for the treatment and mitigation of blood clots and to lower the risk of stroke in individuals with the heart condition known as atrial fibrillation. This medication is specifically indicated for preventing blood clots post hip or knee replacement surgeries and in patients with a prior history of clots. Compared to warfarin, dabigatran serves as a viable alternative that does not necessitate routine blood monitoring tests. The complimentary benefits associated with SALL (salting-out assisted liquid-liquid extraction) and the fluorogenic capabilities of benzofurazan. These methods were combined to provide an affordable and sensitive DBG assaying method. The spectral strength of the yellow luminous product was examined at 533.8nm and by adjustment of a wavelength of 474.7nm for excitation. To assess its linearity, the calibration chart was tested across a DBG concentration range of 30-500 ng/ml. Via accurate computation based on ICH, the detection limit (LD) was determined to be 9.5ng/ml, and the strategy can quantify the DBG to a limit of 28 ng/ml. To ensure success, various crucial parameters for method implementation have been extensively studied and adapted. The validation of the strategy adhered to the policies outlined by ICH, affirming its precision in quantifying DBG in capsules. Furthermore, the inclusion of SALLE steps facilitated accurate monitoring of DBG in plasma samples, introducing a unique and advanced methodology for analyzing this compound in biological samples.

Eco-friendly cobalt-doped carbon quantum dots for spectrofluorometric determination of pregabalin in pharmaceutical capsules

The misuse of pregabalin has become a significant issue over the last decade. Consequently, there is a growing demand for a sensitive and selective method for its determination. In this study, an eco-friendly cobalt-doped carbon quantum dots (CQDs) have been fabricated and applied as nanoprobes for the fluorometric determination of pregabalin. The CQDs were synthesized through mixed doping with non-metallic atoms such as nitrogen and sulfur, and a metal ion, cobaltous ion, via a microwave-assisted method in just 1.5 min. The synthesized Co-NS-CQDs exhibited advantageous characteristics, including rapid response times, compatibility with various pH levels, exceptional detection limits, high sensitivity, and excellent selectivity. The Co-NS-CQDs exhibited a high quantum yield (55 %) relative to NS-CQDs (38 %), with blue emissive light at 438 nm. The assessment of pregabalin was based on its enhancement effect on the native fluorescence intensity of CQDs. The proposed method had a good linearity over the range of 25–250 µg/mL, with a limit of detection of 4.17 µg/mL and a limit of quantitation of 12.63 µg/mL, respectively. The prepared NS-CQDs have been successfully applied for the pregabalin determination in pharmaceutical capsules, with excellent % recovery (98–102 %). The greenness of the developed method has been investigated using different greenness metrics, in comparison with the reported RP HPLC method. The greenness characteristics of the method originated from the synthesis of CQDs, utilizing sustainable, readily available, and cost-effective starting materials.

Development and Validation of a New Reversed Phase HPLC Method for the Quantitation of Azithromycin and Rifampicin in a Capsule Formulation.

This research aimed to develop a new method for simultaneously estimating the presence of azithromycin (AZT) and rifampicin (RIF) in a capsule formulation using reverse-phase high-performance liquid chromatography. The developed method utilized a Gemini column with a 60:40% v/v acetonitrile and potassium dihydrogen phosphate mobile phase, a flow rate of 1mL/min, and an injection volume of 20μL. The detection wavelengths of 210 and 254nm for AZT and RIF, respectively, were used. Validation ensures specificity with a peak purity index > 0.99999 for AZT and >0.99995 for RIF, affirming unambiguous analyte detection. The system suitability test, within acceptable limits, validates method reliability. Linearity calibration curves (R2 = 0.998) cover a 25-150% target concentration range. Accuracy studies employing the standard addition method yield recovery values between 96.6 and 103.9% for both drugs, confirming method accuracy. Precision studies reveal % relative standard deviation values consistently below 2%, highlighting reproducibility. Robustness testing supports method reliability under varying conditions. Application to a pharmaceutical capsule formulation demonstrates the method's practicality, accurately quantifying AZT (98.30%) and RIF (99.37%). This study provides a validated analytical approach for simultaneous quantification in commercial pharmaceutical products containing both drugs, enhancing pharmaceutical quality control for critical antibiotics in complex formulations.

Bismuth oxide and nitrogen-doped reduced graphene oxide co-modified glassy carbon electrode to perform sensitive electrochemical sensing and determination of chrysin in pharmaceutical capsules

A bismuth oxide- nitrogen doped reduced graphene oxide/glassy carbon electrode (Bi2O3-NRGO/GCE) was prepared for the detection of the flavonoid drug chrysin in pharmaceutical capsules, for the first time. Bi2O3 nanosheets synthesized by a hydrothermal method, were ultrasonically mixed with NRGO, and a simple and efficient Bi2O3-NRGO/GCE composite was prepared. The composites were characterized by various methods. Cyclic voltammetry and electrochemical impedance techniques were used to study the electrochemical sensing performance of the composites-modified electrode surface. The electrochemical performance and optimal detection conditions of chrysin on Bi2O3-NRGO/GCE were investigated by differential pulse voltammetry (DPV). The oxidation peak current of chrysin has a linear relationship with its concentration, in the range of 0.01–10 μM, with a detection limit of 2.0 nM. Bi2O3-NRGO/GCE also has good selectivity for chrysin, which is not interfered with by common inorganic salts and common organic substances, or by structurally similar substances. The composite electrode also has good repeatability, reproducibility and stability. It shows that utilizing Bi2O3 and NRGO binary complexes modified electrodes for ultrasensitive chrysin sensing is a simple and convenient detection method, with promising applicability in the development of pharmaceutical component sensing technology.

A Green Voltammetric Determination of Molnupiravir Using a Disposable Screen-Printed Reduced Graphene Oxide Electrode: Application for Pharmaceutical Dosage and Biological Fluid Forms

A new green-validated and highly sensitive electrochemical method for the determination of molnupiravir (MOV) has been developed using cyclic voltammetry. The proposed analytical platform involves the use of a disposable laboratory-made screen-printed reduced graphene oxide 2.5% modified electrode (rGO-SPCE 2.5%) for the first time to measure MOV with high specificity. The surface morphology of the sensor was investigated by using a scanning electron microscope armed with an energy-dispersive X-ray probe. The fabricated sensor attained improved sensitivity when sodium dodecyl sulfate (SDS) surfactant (3 µM) was added to the supporting electrolyte solution of 0.04 M Britton–Robinson buffer at pH 2. The electrochemical activity of rGO-SPCE was examined in comparison with two different working electrodes in order to demonstrate that it was the most competitive sensor for MOV monitoring. The method was validated using differential pulse voltammetry according to ICH guidelines, resulting in good precision, accuracy, specificity, and robustness over a concentration range of 0.152–18.272 µM, with a detection limit of 0.048 µM. The stability investigation demonstrated that rGO-SPCE 2.5% can provide high-stability behavior towards the analyte throughout a six-week period under refrigeration. The fabricated rGO-SPCE 2.5% was successfully employed for the measurement of MOV in pharmaceutical capsules and human biofluids without the interference of endogenous matrix components as well as the commonly used excipient.

New HPLC method for determination of fluvastatin anti-hyperlipidemic drug in bulk and pharmaceutical dosage using simvastatin as internal standard

A new, and reliable RP–HPLC method has been investigated and validated for the assay of fluvastatin sodium (FVS) in pharmaceutical capsules. The chromatographic method was carried out using an ODS Hypersil C18 column (250×4.6 mm i.d., 5 µm particle size); a mixture containing methanol and 0.10 M ammonium acetate (70:30, v/v), a flow rate 1.0 mL/min and UV detection at 305 nm. The retention time for fluvastatin and the internal standard simvastatin (SVS) was found to be 3.2 and 6.4 minutes, respectively. Despite the wide range of the analyte concentration, the method showed good linearity (r&gt;0.9998) in the range 2.0–320.0 µg mL-1. The proposed method was validated with respect to linearity, accuracy, precision, and robustness. The limit of detection was 0.54 µg mL-1. The successful application of the new HPLC method indicates its routine use to quantify of FVS in pharmaceuticals.

Synchronous fluorescence as a green and selective method for the simultaneous determination of finasteride and tadalafil in dosage form and spiked human plasma

Finasteride and tadalafil are combined in a pharmaceutical capsules called Entadfi™, that has received FAD approval. It was indicated for the management of male benign prostatic hyperplasia-related urinary tract issues. In the current study, finasteride and tadalafil concentrations in raw form, laboratory prepared mixtures, pharmaceutical preparation and spiked human plasma were all quantitatively estimated using a sensitive synchronized fluorescence spectroscopic approach united with first derivative. When excited at 260 nm, finasteride display its emission at 320 nm. Yet, when excited at 280 nm, tadalafil displayed its emission at 340 nm. The application of micellar surfactant as sodium dodecyl sulphate (SDS) significantly increased the fluorescence intensity.The overlapping of the fluorescence spectra was entirely eliminated by derivatizing the synchronous spectra to the first derivative, which also made it possible to simultaneously quantify the cited drugs. Without interfering with one another, the first-order synchronous spectra of tadalafil and finasteride at 320 and 330 nm, respectively. The approach revealed linearity alongside an acceptable correlation coefficient for finasteride and tadalafil concentrations over the range of 10 –50 ng/mL. That approach was utilized to estimation of the cited drugs in dosage forms, simultaneously with %recoveries for tadalafil and finasteride of 99.62 ± 0.78 and 100.19 ± 0.60, respectively. Also, four various tools, the national environmental method index, the AGREE evaluation method, the green analytical procedure index and the analytical eco-scale were used to evaluate how environmentally friendly the given approach was. With regard to the metrics of the greenness aspects, the proposed approach appeared to be better than the previously published spectrophotometric methods and HPLC.

A novel spectrophotometric approach relies on a charge transfer complex between atomoxetine with quinone-based π-acceptor. Application to content uniformity test

Atomoxetine (ATO) belongs to psychoanaleptic drugs and is utilized in attention-deficit hyperactivity syndrome treatment. In this study, two facile and selective approaches are implemented for the spectrophotometric analysis of atomoxetine. The two approaches rely on charge transfer formed between ATO base (n-donor) with p-chloranil and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ; π-acceptor). The generated complexes exhibit absorption intensity maxima at 550 and 460 nm in acetonitrile for p-chloranil and DDQ in the order. Under the optimum reaction condition, Beer’s law was followed for p-chloranil and DDQ at concentrations of 30–320 and 10–80 µg mL− 1, respectively. The ICH guidelines were followed for work validation, and the outcomes were excellent and satisfactory. The assessment of ATO in pharmaceutical capsules using the suggested procedures was successful, and the results were contrasted with those obtained using a different published method to show accuracy and precision. Additionally, the two methods were used to assess the homogeneity of ATO content in the commercialized capsule.

Micellar-enhanced and green-assessed first-derivative synchronous spectrofluorimetric approach for concurrent determination of alfuzosin hydrochloride and solifenacin succinate in different matrices: Docking simulation

Alfuzosin hydrochloride (AZH) is co-formulated with solifenacin succinate (SOS) in Solitral® capsules for treating prostate hyperplasia in patients with overactive bladder syndrome. Herein and for the first time, an ultrasensitive synchronous spectrofluorimetric approach coupled with first-order derivative signal processing was designed for simultaneous determination of AZH and SOS in their pure forms, newly-released pharmaceutical capsules, and human biological fluids. AZH and SOS showed their conventional emission spectra in bi-distilled water at 382 nm and 294 nm after excitation at 325 nm and 250 nm, respectively. The native fluorescence intensities of AZH and SOS were greatly enhanced through micellar formation using sodium dodecyl sulfate surfactant (2%). The proposed approach included the use of synchronous mode at Δλ of 60 nm where the overlap between the studied analytes’ fluorescence spectra wasn't completely resolved. The complete resolution was achieved by derivatization of the synchronized spectra to the first-order yielding two zero-crossing points which allowed the determination of AZH and SOS simultaneously without interference at 408 nm and 321 nm, respectively. Under optimum experimental circumstances, good linearities were accomplished over the concentration ranges of (1–24) ng/mL and (4–250) ng/mL with LOD of 0.26 ng/mL and 1.31 ng/mL for AZH and SOS, respectively. The proposed approach was validated successfully according to guidelines adopted by the ICH and compared statistically with the reported LC method with no discernible differences concerning accuracy or precision at p = 0.05. Successful application of the proposed approach achieved with excellent recovery percentages for analysis of the studied analytes in different matrices (pharmaceutical capsules and biological fluids) confirms its suitability for use in QC laboratories and other bioanalytical applications. The proposed approach’s greenness was evaluated using two tools namely; penalty points scoring system and green analytical procedure index (GAPI) divulging excellent greenness of this approach relative to the reported LC method. The proposed approach relied chiefly on water as the cheapest and greenest solvent.

Evaluation of the self-healing capacity of concrete with low-cost macro-capsules

This study focuses on the evaluation of the efficiency of a low-cost macrocapsule, using commercially available pharmaceutical capsules with specific modifications, for self-healing concrete. The macrocapsules were developed by the Belgian Building Research Institute in a previous study. The healing agent is a resin based on alkyd-urethane, a low-cost commercial product, which was selected for its compatibility with concrete and shell, and also for the following reasons: resin release, adhesion to concrete, and reduction in capillary water absorption. After their manufacturing, the macrocapsules were carefully integrated within the concrete mix at 5 volume-%, and cubes and slabs for compressive and impact tests were cast. Small beams 160 x 40 x 40 mm3 containing each three capsules (placed 15 mm above the bottom surface) were tested for flexural strength and capillary water absorption. The effect of self-healing was evaluated by sorptivity test for two different crack mouth opening displacements of 0.5 mm and 0.9 mm. In both cases, the cracks were partially or completely healed, and the mechanical properties of the macrocapsule specimens were quite the same as the reference specimens. This demonstrates that the modified low-cost macrocapsules are sufficient to heal large cracks without losing the concrete mechanical properties.

Chicken Bones As Gelatin Source For Pharmaceutical Preparations

This study primarily aimed to extract gelatin from chicken bones which could be used as basic raw material for pharmaceutical capsule preparation. The processing of the raw, fresh bones into gelatin involved the following stages: degreasing/defatting, demineralization, conditioning and pretreatment, extraction, drying, grinding to the desired grain size, packing in airtight containers. The gelatin obtained is yellowish in color, has a slight but not disagreeable odor and is stable on dry air. It is insoluble in cold water, but dissolves readily in hot water. It is slightly soluble in acetic acid and alcohol but soluble in hot solution of glycerine and water. It is insoluble in organic solvents such us ether, chloroform and mineral oil. Its viscosity is 1.1816 poise. Based on the USP and Merck’s requirement for Identification Test for commercial gelatin, the gelatin obtained from chicken bones passed the standard set up. For the Microbial Limits Determination, the chicken bone gelatin did not exceed the total plate count of 1,000 microbes per gram of sample. The determination of gelatin-water concentration for capsule preparation showed that the 1:1.5 concentrations suited best which was supported from ITDI Pigskin/bones gelatin results. In conclusion, chicken bones are therefore good source of gelatin using petroleum ether as solvent.

A Mid-Infrared Spectrophotometric Method for Simultaneous Quantification of Naltrexone and Bupropion with Multivariate Calibration

Naltrexone (NTX) and bupropion (BUP) are used in combination in clinical practice for obesity; however, the existing analytical methods for this drug combination are not sustainable. This work aims to develop an analytical method that is faster, easier and less expensive compared with high performance liquid chromatography (HPLC) and involves green technology without solvents to quantify BUP and NTX in combination. The objective was to validate a method using mid-infrared (MIR) spectroscopy associated with multivariate calibration and chemometrics to simultaneously measure NTX and BUP in a pharmaceutical capsule form. The models were developed using MIR spectroscopy with diffuse reflectance, with interval partial least squares (iPLS) variable selection. The working range selected to optimize the model was from 1885.8 to 1585.4 cm-1. The chosen model was obtained with partial least squares (PLS2) and with data pre-processed by first derivative Savitzky-Golay smoothing followed by mean centering, using four latent variables, providing a root mean square error of prediction of 1.8 mg g-1 for NTX and 6.42 mg g-1 for BUP. The method was validated according to current international standards. In conclusion, the methods developed in the MIR region provided statistically similar results to the validated chromatographic method for commercial pharmaceutical formulations.

Surface Quality Automatic Inspection for Pharmaceutical Capsules Using Deep Learning

Capsules are commonly used as containers for most pharmaceutical products. Thus, the quality of a capsule is closely related to the therapeutic effect of the products and patient health. At present, surface quality testing is an essential task in the actual production of pharmaceutical capsules. In this study, a deep learning-based capsule defect detection model, called CapsuleDet, is proposed to classify and localize defects in image sensor data from capsule production for practical application. A guided filter-based image enhancement method and hybrid data augmentation method are used in improving the quality and quantity of the raw data, respectively, to mitigate the low contrast issue and enhance the robustness of the model training. Deformable convolution module and attentional fusion feature pyramid are also used to improve the detection effect of capsule defects by effectively utilizing the semantic and geometric information in the extracted feature maps and catering to the detection of defects with different shapes and scales. The evaluation results on the capsule defect dataset demonstrate that the proposed method achieves 92.91% mean average precision and 22.16 frames per second. Moreover, its overall performance in terms of training time, model size, detection accuracy, and speed is better than that of the currently popular detectors.

Simultaneous spectrophotometric determination of finasteride and tadalafil in recently FDA approved Entadfi™ capsules

Entadfi™ is a recently FDA approved pharmaceutical combination capsule of finasteride and tadalafil. It was prescribed for the treatment of urinary tract disorders caused by benign prostatic hyperplasia in men. This paper introduced the first spectrophotometric methods for simultaneous determination of finasteride and tadalafil in the pure form and in the pharmaceutical capsules. UV absorption spectra of finasteride and tadalafil exhibited overlap hindered the direct simultaneous determination of the cited drugs. The UV absorption spectra of finasteride and tadalafil were transformed to the second order derivative. Finasteride could be determined selectively at 230.80 nm without interference from tadalafil. Moreover, tadalafil could be determined selectively at 292 nm without interference from finasteride. The ratio spectra of the studied drugs were derived and the derived ratio spectra of each drug were transformed to the first order derivative. Finasteride could be determined selectively at 218.80 nm without interference from tadalafil. Moreover, tadalafil could be determined selectively at 289.60 nm without interference from finasteride. The methods showed linearity with an excellent correlation coefficient in the concentration range of 10–140 µg/mL for finasteride and 3–40 µg/mL for tadalafil. The methods were validated following ICH guidelines for accuracy, precision, robustness, limit of detection, limit of quantification, and selectivity. The methods were found to be sensitive with LOD values for finasteride and tadalafil of 2.406 µg/mL and 0.876 µg/mL using the second derivative with zero crossing method and 2.229 µg/mL and 0.815 µg/mL using the first derivative of ratio spectra method. The methods were successfully applied for the determination of the studied drugs in their laboratory prepared mixtures, with mean percent recovery for finasteride and tadalafil of 99.37% and 99.17% using the second derivative with zero crossing method and 99.74% and 99.56% using the first derivative of ratio spectra method. Furthermore, the described methods were successfully applied for determination of the studied drugs in Entadfi™ capsules without interference from excipients. Based on the proposed results, the described methods could be utilized as simple method for the quality control of the studied drugs.