Search Results (18)

Medicinal products available on the market should be characterised by therapeutic efficacy, high quality, and safety for patients. They must either be sterile or comply with the appropriate pharmacopoeial microbiological purity requirements. Pharmacopoeial monographs related to microbiological tests of drug quality were also referenced. Despite stringent regulations governing pharmaceutical production, irregularities in the microbiological quality of drugs still occur. These are monitored by relevant agencies, which may order the recall of defective product batches from the market. However, in recent years, numerous cases of microbiological contamination in drugs and drug-related infections have been reported. Both isolated incidents and larger outbreaks or epidemics linked to contaminated medicines have been documented. Various microorganisms, including Gram-negative and Gram-positive bacteria, anaerobes, and yeast-like and mould fungi, have been identified in medicinal products or in patients affected by contaminated drugs. Ensuring the appropriate purity or sterility of pharmaceutical raw materials; maintaining cleanliness in the manufacturing environment, facilities, and equipment; and adhering to hygiene protocols and Good Manufacturing Practice regulations are essential for the production of safe and high-quality medicinal products. The aim of this study is to collect and compile information on the microbiological quality of drugs available on the market, with particular attention to identified irregularities, objectionable microorganisms isolated from medicinal products, and drug-related infections. Full article

The objective of the conducted research was to design 2 mm orodispersible minitablets of pediatric doses of hydrocortisone (0.5 mg; 1.0 mg) with desirable pharmaceutical properties and eliminate the sensation of a bitter taste using preparation of solid dispersion by ball mill. Hydrocortisone was selected as the model substance, as it is widely utilized in the pediatric population. ODMTs were prepared by compression (preceded by granulation) in a traditional single-punch tablet machine and evaluated using pharmacopoeial tests, DSC, and FTIR analysis. The methods used to evaluate the effectiveness of the taste-masking effect included in vivo participation of healthy volunteers, in vitro drug dissolution and utilization of an analytical device—“electronic tongue”. The research employed a preclinical animal model to preliminary investigate the bioequivalence of the designed drug dosage form in comparison to reference products. The study confirmed the possibility of manufacturing good-quality hydrocortisone ODMTs with a taste-masking effect owing to the incorporation of a solid dispersion in the tablet mass. Full article

Naproxen is one of the most used non-steroidal anti-inflammatory drugs (NSAIDs). It is used to treat pain of various origins, inflammation and fever. Pharmaceutical preparations containing naproxen are available with prescription and over-the-counter (OTC). Naproxen in pharmaceutical preparations is used in the form of acid and sodium salt. From the point of view of pharmaceutical analysis, it is crucial to distinguish between these two forms of drugs. There are many costly and laborious methods to do this. Therefore, new, faster, cheaper and, at the same time, simple-to-perform identification methods are sought. In the conducted studies, thermal methods such as thermogravimetry (TGA) supported by calculated differential thermal analysis (c-DTA) were proposed to identify the type of naproxen in commercially available pharmaceutical preparations. In addition, the thermal methods used were compared with pharmacopoeial methods for the identification of compounds, such as high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), UV-Vis spectrophotometry, and a simple colorimetric analyses. In addition, using nabumetone, a close structural analog of naproxen, the specificity of the TGA and c-DTA methods was assessed. Studies have shown that the thermal analyses used are effective and selective in distinguishing the form of naproxen in pharmaceutical preparations. This indicates the potential possibility of using TGA supported by c-DTA as an alternative method. Full article

Polygoni Cuspidati Rhizoma et Radix (syn. rhizomes of Reynoutria japonica Houtt.) is a pharmacopoeial raw material in Europe and China. In traditional medicine, one of the applications for Reynoutria japonica rhizomes is wound healing. In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope—CLSM), and cell migration (wound healing assay). Moreover, the collagen type III expression was examined using immunocytochemical staining. The studied decoction was qualitatively and quantitatively characterized using the validated HPLC/DAD/ESI-HR-QTOF-MS method. The Folin–Ciocalteu assay was used to determine the total phenols and tannins content. Additionally, HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts was used to determine the composition of saccharides. Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. No cytotoxic effect was observed at any tested concentration (up to 2000 µg/mL). The lowest active concentration of decoction (50 µg/mL) was selected for further experiments. It significantly stimulated human gingival fibroblasts to proliferate, migrate, and increase the synthesis of collagen III. Phytochemical analysis showed significantly fewer polyphenols in the decoction than in the ethanol and acetone extracts tested earlier. In contrast, high levels of polysaccharides were observed. In our opinion, they may have a significant effect on the oral wound healing parameters analyzed in vitro. The results obtained encourage the use of this raw material in its traditional, safe form—decoction. Full article

Praziquantel is a poorly water-soluble drug used to treat parasitic infections. Previous studies have suggested that its rate and extent of dissolution in milk and biorelevant media are slow and limited compared to dissolution in the pharmacopoeial-recommended medium, despite being reported as displaying a positive food effect upon administration. This study aimed to revisit the dissolution of praziquantel in biorelevant media and milk to better understand this apparent dichotomy. The context of digestion was introduced to better understand drug solubilisation under more relevant gastrointestinal conditions. The amount of praziquantel solubilised in the various media during digestion was quantified using high performance liquid chromatography (HPLC) and the kinetics of dissolution were confirmed by tracking the disappearance of solid crystalline drug using in situ small angle X-ray scattering (SAXS). For the dissolution media, where sodium lauryl sulfate (SLS) is typically included as a wetting agent, a prominent effect of SLS on drug dissolution was also apparent where >2.5 fold more drug was solubilised in SLS-containing dissolution medium compared to that without (0.1 M HCl only). In milk, significant dissolution of praziquantel was observed only during digestion and not during dispersion, hence suggesting that (1) milk can be potentially administered with praziquantel to improve oral bioavailability and (2) incorporating a digestion step into existing in vitro dissolution testing can better reflect the potential for a positive food effect when lipids are present. Full article

The in vitro release of theophylline from an extended-release dosage form was studied under different hydrodynamic conditions in a United States Pharmacopoeial (USP) dissolution system II and a bespoke in vitro tubular model of the human colon, the Dynamic Colon Model (DCM). Five biorelevant motility patterns extracted from in vivo data were applied to the DCM, mimicking the human proximal colon under baseline conditions and following stimulation using polyethylene glycol or maltose; these represent the lower and upper bounds of motility normally expected in vivo. In the USPII, tablet dissolution was affected by changing hydrodynamic conditions at different agitation speeds of 25, 50 and 100 rpm. Applying different motility patterns in the DCM affected the dissolution profiles produced, with theophylline release at 24 h ranging from 56.74 ± 2.00% (baseline) to 96.74 ± 9.63% (maltose-stimulated). The concentration profiles of theophylline were markedly localized when measured at different segments of the DCM tube, highlighting the importance of a segmented lumen in intestine models and in generating spatial information to support simple temporal dissolution profiles. The results suggested that the shear stresses invoked by the unstimulated, healthy adult human colon may be lower than those in the USPII at 25 rpm and thus insufficient to achieve total release of a therapeutic compound from a hydroxyethyl cellulose matrix. When operated under stimulated conditions, drug release in the DCM was between that achieved at 25 and 50 rpm in the USPII. Full article

Confirmation of the composition of pharmaceutical products is an essential pharmaceutical issue. The purity and identity of active pharmaceutical ingredients (API) in the finished drug impact the effect of correct and safe pharmacotherapy. The currently frequently used advanced analytical methods are laborious and time-consuming. On the other hand, less advanced techniques such as UV-Vis spectrophotometry are less specific. In the presented study, thermogravimetry analysis (TGA)—supported by calculated differential thermal analysis (c-DTA)—was proposed to evaluate the composition of pharmaceutical preparations containing theophylline and aminophylline. Due to its advantages, the TGA method can be an alternative used for screening assessment of the composition of pharmaceutical preparations. The obtained results show that TGA supported by c-DTA is a suitable screening method for assessing the composition of pharmaceutical preparations containing theophylline and aminophylline. Both thermal techniques complement each other to obtain reliable results. In contrast to the pharmacopoeial UV-Vis method, TGA allows for unambiguous identification and distinction of one- and two-component pharmaceutical preparations. Moreover, thanks to TGA and c-DTA, it was possible to identify the excipient used in the formulation of a commercial drug and to detect considerable amounts of lactose in the experimentally prepared counterfeit formulation. The research herein indicates the multifaceted application and usefulness of TGA and c-DTA in pharmacology. Full article

Dose administration aids (DAAs) are commonly used to assist patients with chronic disease to manage multiple medications and thus improve adherence. Several brands of telmisartan, commonly prescribed for hypertension, are available in Australia. Manufacturer’s storage advice is to leave tablets in the blister strip until administered to patients. This study aimed to investigate the stability of telmisartan tablets when repackaged and stored in DAAs, to identify a brand, which is sufficiently stable to be repackaged. All available brands of telmisartan tablets in Australia, which contain different excipients, were repackaged into DAAs and stored at 30 °C, 75% RH for 28 days before screening, using visual inspection and physical testing. A candidate brand was then selected for physicochemical and photostability testing using pharmacopoeial methods. Repackaged Mizart^® tablets were shown to be sufficiently stable, when repackaged and stored under tropical conditions (30 °C, 75% RH) for 28 days. Several of the other brands were deemed inappropriate for repackaging, due to physical instability, highlighting the importance of considering not only the drug, but also excipients to ensure the stability of repackaged medicines. Although the repackaging of telmisartan tablets is not advised, this study provides evidence to support the Mizart^® brand as an option for pharmacists to recommend for repackaging. Full article

Determination of valproic acid in the drug was carried out on the aluminum silica gel 60F₂₅₄ plates and using acetone–water–chloroform–ethanol–ammonia at a volume ratio of 30:1:8:5:11 as the mobile phase, respectively. Two methods of detection of valproic acid were used. The first was a 2% aqueous CuSO₄×5H₂O solution, and the second was a 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system. The applied TLC-densitometric method is selective, linear, accurate, precise, and robust, regardless of the visualizing reagent used for the determination of valproic acid in Convulex capsules. It has low limits of detection (LOD) and limits of quantification (LOQ), which are equal to 5.8 μg/spot and 17.4 μg/spot using a 2% aqueous CuSO₄×5H₂O solution as visualizing agent and also 0.32 μg/spot and 0.97 μg/spot using a 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system as visualizing reagent, respectively. The described analytical method can additionally be used to study the identity of valproic acid in a pharmaceutical preparation. The linearity range was found to be 20.00–80.00 μg/spot and 1.00–2.00 μg/spot for valproic acid detected on chromatographic plates using a 2% aqueous CuSO₄×5H₂O solution and the 2′,7′-dichlorofluorescein-aluminum chloride-iron (III) chloride system, respectively. A coefficient of variation that was less than 3% confirms the satisfactory accuracy and precision of the proposed method. The results of the assay of valproic acid equal 96.2% and 97.0% in relation to the label claim that valproic acid fulfill pharmacopoeial requirements. The developed TLC-densitometric method can be suitable for the routine analysis of valproic acid in pharmaceutical formulations. The proposed TLC-densitometry may be an alternative method to the modern high-performance liquid chromatography and square wave voltammetry in the control of above-mentioned substances, and it can be applied when other analytical techniques is not affordable in the laboratory. Full article

Modern pharmaceutical technology still seeks new excipients and investigates the further use in already known ones. An example is magnesium aluminometasilicate Neusilin^® US2 (NEU), a commonly used inert filler with unique properties that are usable in various pharmaceutical fields of interest. We aimed to explore its application in hypromellose matrix systems (HPMC content 10–30%) compared to the traditionally used microcrystalline cellulose (MCC) PH 102. The properties of powder mixtures and directly compressed tablets containing individual fillers NEU or MCC, or their blend with ratios of 1.5:1, 1:1, and 0.5:1 were investigated. Besides the routine pharmaceutical testing, we have enriched the matrices’ evaluation with a biorelevant dynamic dissolution study and advanced statistical analysis. Under the USP apparatus 2 dissolution test, NEU, individually, did not provide advantages compared to MCC. The primary limitations were the burst effect increase followed by faster drug release at the 10–20% HPMC concentrations. However, the biorelevant dynamic dissolution study did not confirm these findings and showed similarities in dissolution profiles. It indicates the limitations of pharmacopoeial methods in matrix tablet development. Surprisingly, the NEU/MCC blend matrices at the same HPMC concentration showed technologically advantageous properties. Besides improved flowability, tablet hardness, and a positive impact on the in vitro drug dissolution profile toward zero-order kinetics, the USP 2 dissolution data of the samples N75M50 and N50M50 showed a similarity to those obtained from the dynamic biorelevant apparatus with multi-compartment structure. This finding demonstrates the more predictable in vivo behaviour of the developed matrix systems in human organisms. Full article

Optimization of transdermal formulations requires solving simultaneous challenges as the selection of release polymers. The interactions between the formulation components must be taken as a way to modulate its performance. Selection of acrylic polymers with different functionalizations for the transdermal formulation of a tertiary amine drug (ropinirole HCl) have been investigated. Aim of this work is to characterize the influence over drug release of certain experimental interactions. Solubility-crystalization and pharmacopoeial release tests have been used to evaluate the influence of drug loading and the pH of the release media. Area under the curve of dissolved amounts and percentage of release have been used as discriminant variables in mutual influence with the physical state of the drug. Elucidation of release mechanisms has been performed with data fitting of relevant modelystic equations. Fickian release and erosion contribution have been related with drug loading and the risk of burst effects. In conclusion, a rationale to select the best suitable polymer for ropinirole HCl has been demonstrated in terms of efficiency and extent of release. Full article

The production of orodispersible films (ODFs) with suspended insoluble drug substances is still a challenge, mainly due to the difficulty associated with achieving a proper homogeneity and mechanical properties of the films. Hypromellose (HPMC) and a mixture of polyvinyl alcohol (AP) and povidone (PVP) were compared in terms of their suitability for ODFs incorporating suspended micronized loratadine (LO) in a concentration range of 10%–40%. In a planetary mixer (Thinky), a uniform dispersion of LO in an aqueous viscous casting solution was obtained. The suspended LO particles caused dose-dependent changes in the viscosity of the casting mass and affected the mechanical quality of ODFs. Drug concentrations higher than 30% reduced the film flexibility and tear resistance, depending on the polymer type. LO films with a thickness of 100 µm disintegrated within 60-100 s, with no significant influence of the LO content in the range 10%–30%. HPMC films, regardless of the drug concentration, met the pharmacopoeial requirements regarding the uniformity of the drug content. AP/PVP films were too elastic, and the drug content uniformity was not achieved. The conclusion is that, using an HPMC matrix, it is possible to obtain a high load of a poorly water-soluble drug (30% of dry film mass corresponds to a dose of 5 mg per 1.5 cm²) in ODFs characterized by proper physical characteristics. Full article

New strategies are continuously sought for the treatment of skin and wound infections due to increased problems with non-healing wounds. Electrospun nanofiber mats with antibacterial agents as drug delivery systems provide opportunities for the eradication of bacterial infections as well as wound healing. Antibacterial activities of such mats are directly linked with their drug release behavior. Traditional pharmacopoeial drug release testing settings are not always suitable for analyzing the release behavior of fiber mats intended for the local drug delivery. We tested and compared different drug release model systems for the previously characterized electrospun chloramphenicol (CAM)-loaded nanofiber (polycaprolactone (PCL)) and microfiber (PCL in combination with polyethylene oxide) mats with different drug release profiles. Drug release into buffer solution and hydrogel was investigated and drug concentration was determined using either high-performance liquid chromatography, ultraviolet-visible spectrophotometry, or ultraviolet (UV) imaging. The CAM release and its antibacterial effects in disc diffusion assay were assessed by bacterial bioreporters. All tested model systems enabled to study the drug release from electrospun mats. It was found that the release into buffer solution showed larger differences in the drug release rate between differently designed mats compared to the hydrogel release tests. The UV imaging method provided an insight into the interactions with an agarose hydrogel mimicking wound tissue, thus giving us information about early drug release from the mat. Bacterial bioreporters showed clear correlations between the drug release into gel and antibacterial activity of the electrospun CAM-loaded mats. Full article

Endotoxins are cell wall components of Gram-negative bacteria. A release of endotoxins into the human blood stream results in an inflammation reaction that can lead to life-threatening conditions like sepsis. Therefore, control for endotoxin contamination of intravenously administered drugs is crucial. Drugs are usually tested for putative endotoxin contamination with Limulus-based tests. However, validity of the compendial test procedures is questioned in the case of low endotoxin recovery (LER). To assure validity, regulatory authorities request hold-time studies of endotoxin in addition to pharmacopoeial requirements. Within these studies, endotoxin is added (spiked) to an undiluted product. The spiked product is held for a certain period of time and subsequently diluted for endotoxin determination. Due to the known heterogeneity of endotoxin the question has been raised as to which source represents the most adequate endotoxin spike. In the present study, endotoxin hold-time studies were analyzed by using different sources of endotoxin. Highly purified endotoxin, crude endotoxin extracts (Naturally Occurring Endotoxin) from different bacterial species and varied growth conditions as well as endogenous endotoxin contaminations were investigated. The results clearly demonstrate that endotoxin masking—an effect of LER—is dependent on the endotoxin source used. Various parameters such as bacterial strain and growth conditions lead to different masking susceptibilities. Due to these effects it is impossible to predict the susceptibility of bacterial endotoxin contamination to LER. In order to determine whether a sample is prone to LER, an endotoxin spike that is susceptible to LER is required. Full article

This study reports the development and validation of a new, simple, and accurate high-performance thin-layer chromatography (HPTLC)-densitomeric method for the determination of nandrolone decanoate in a commercially available injection formulation. Chromatographic analysis was performed on glass CN modified silica gel 60F₂₅₄ plates developed using n-hexane-ethyl acetate in volume ratio 42.5:7.5 as the mobile phase. Densitometric scanning was carried out at the wavelength of 245 nm. This chromatographic system gave compact spot and a symmetrical peak of nandrolone decanoate with retardation factor (R_F) value at 0.57 (±0.02). The linearity of this method with the high correlation coefficient of calibration plot ranges from 0.780 to 12.500 μg/spot. The developed method is characterized by good precision (coefficient of variation CV < 2%) and high accuracy close to 100.3% (R = 99.0%). Values of limits of detection and quantification equal to 0.231 and 0.700 μg/spot, respectively, confirm the sensitivity of the developed method. The analysis of the pharmaceutical formulation of nandrolone decanoate indicates drug content of 50.5 mg/mL and 101.0% in relation to the label claim. This is in good agreement with the recommendation of the International Council for Harmonisation (ICH) guidelines as well as the pharmacopoeial requirements. The low CV value (<1%) of nandrolone decanoate content in the tested injection formulation confirms the suitability of the proposed HPTLC-densitometric method for routine control of this compound in examined pharmaceuticals. Full article