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Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly... (Review)
Review
Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the "spring and parachute" strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug's bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.
Topics: Biological Availability; Humans; Solubility; Emulsions; Lipids; Chemical Precipitation; Pharmaceutical Preparations; Chemistry, Pharmaceutical; Drug Compounding; Polymers; Drug Delivery Systems; Excipients; Animals
PubMed: 38815207
DOI: 10.2478/acph-2024-0023 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024At present, society has embraced the fact apropos population aging and climate changes, that demand, amongst others, innovative pharmaceutical technologies, emphasising...
At present, society has embraced the fact apropos population aging and climate changes, that demand, amongst others, innovative pharmaceutical technologies, emphasising the development of patient-specific delivery systems and thus the provision of efficient and sustainable drugs. Protein drugs for subcutaneous administration, by allowing less frequent application, represent one of the most important parts of the pharmaceutical field, but their development is inevitably faced with obstacles in providing protein stability and suitable formulation viscosity. To gain further knowledge and fill the gaps in the already constructed data platform for the development of monoclonal antibody formulations, we designed a study that examines small model proteins, bovine serum albumin. The main aim of the presented work is to evaluate the effect of protein concentrations on critical quality attributes of both, pre-lyophilised liquid formulations, and lyophilised products. Through the study, the hypothesis that increasing protein concentration leads to higher viscosity and higher reconstitution time without affecting the stability of the protein was confirmed. The most important finding is that sucrose plays a key role in the lyophilisation of investigated protein, nevertheless, it can be predicted that, to ensure the beneficial effect of mannitol, its amount has to prevail over the amount of sucrose.
Topics: Freeze Drying; Serum Albumin, Bovine; Viscosity; Drug Compounding; Humans; Sucrose; Drug Stability; Chemistry, Pharmaceutical; Excipients; Mannitol; Protein Stability
PubMed: 38815206
DOI: 10.2478/acph-2024-0013 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024In the past, the administration of medicines for children mainly involved changes to adult dosage forms, such as crushing tablets or opening capsules. However, these... (Review)
Review
In the past, the administration of medicines for children mainly involved changes to adult dosage forms, such as crushing tablets or opening capsules. However, these methods often led to inconsistent dosing, resulting in under- or overdosing. To address this problem and promote adherence, numerous initiatives, and regulatory frameworks have been developed to develop more child-friendly dosage forms. In recent years, multiparticulate dosage forms such as mini-tablets, pellets, and granules have gained popularity. However, a major challenge that persists is effectively masking the bitter taste of drugs in such formulations. This review therefore provides a brief overview of the current state of the art in taste masking techniques, with a particular focus on taste masking by film coating. Methods for evaluating the effectiveness of taste masking are also discussed and commented on. Another important issue that arises frequently in this area is achieving sufficient dissolution of poorly water-soluble drugs. Since the simultaneous combination of sufficient dissolution and taste masking is particularly challenging, the second objective of this review is to provide a critical summary of studies dealing with multiparticulate formulations that are tackling both of these issues.
Topics: Taste; Solubility; Humans; Drug Compounding; Pharmaceutical Preparations; Dosage Forms; Chemistry, Pharmaceutical; Tablets; Administration, Oral; Child; Excipients; Drug Liberation
PubMed: 38815202
DOI: 10.2478/acph-2024-0015 -
Scientific Reports May 2024Chemical processing is among the significant keys to tackle agro-residues utilization field, aiming to obtain value-added materials. Extraction of cellulose nanocrystals...
Chemical processing is among the significant keys to tackle agro-residues utilization field, aiming to obtain value-added materials. Extraction of cellulose nanocrystals (CNCs) is an emerging route to valorize lignocellulosic wastes into high value particles. In this investigation, effect of acidic hydrolysis duration was monitored on size and morphology of obtained crystals; namely: CNCs from Nile roses fibers (NRFs) (Eichhornia crassipes). Different acidic hydrolysis duration range or different characterization techniques set this article apart from relevant literature, including our group research articles. The grinded NRFs were firstly subjected to alkaline and bleaching pretreatments, then acid hydrolysis process was carried out with varied durations ranging from 5 to 30 min. Microcrystalline cellulose (MCC) was used as reference for comparison with NRFs based samples. The extracted CNCs samples were investigated using various techniques such as scanning electron microscopy (SEM), Atomic force microscopy (AFM), Raman spectroscopy, and thermogravimetric (TGA) analysis. The figures gotten from SEM and AFM depicted that NRFs based CNCs appeared as fibril-like shapes, with reduced average size when the NRFs underwent pulping and bleaching processes. This was indicated that the elimination of hemicellulose and lignin components got achieved successfully. This outcome was proven by chemical composition measurements and TGA/DTG curves. On the other hand, AFM-3D images indicated that CNCs topology and surface roughness were mostly affected by increasing hydrolysis durations, besides smooth and homogeneous surfaces were noticed. Moreover, Raman spectra demonstrated that the particle size and crystallinity degree of NRFs based CNCs can be affected by acidic hydrolysis durations and optimum extraction time was found to be 10 min. Thermal stability of extracted CNCs-NRFs and CNCs-MCC was measured by TGA/DTG and the kinetic models were suggested to identify the kinetic parameters of the thermal decomposition of CNCs for each acid hydrolysis duration. Increasing hydrolysis duration promoted thermal stability, particularly for NRFs based CNCs. Results showcased in this article add new perspective to Nile rose nanocellulose and pave down the way to fabricate NRFs based humidity nano-sensors.
Topics: Cellulose; Nanoparticles; Eichhornia; Hydrolysis; Microscopy, Atomic Force; Spectrum Analysis, Raman; Microscopy, Electron, Scanning; Thermogravimetry; Lignin
PubMed: 38811644
DOI: 10.1038/s41598-024-62159-z -
Acta Pharmaceutica Sinica. B May 2024Diabetes, characterized by hyperglycemia, is a major cause of death and disability worldwide. Peptides, such as insulin and glucagon-like peptide-1 (GLP-1) analogs, have... (Review)
Review
Diabetes, characterized by hyperglycemia, is a major cause of death and disability worldwide. Peptides, such as insulin and glucagon-like peptide-1 (GLP-1) analogs, have shown promise as treatments for diabetes due to their ability to mimic or enhance insulin's actions in the body. Compared to subcutaneous injection, oral administration of anti-diabetic peptides is a preferred approach. However, biological barriers significantly reduce the efficacy of oral peptide therapeutics. Recent advancements in drug delivery systems and formulation techniques have greatly improved the oral delivery of peptide therapeutics and their efficacy in treating diabetes. This review will highlight (1) the benefits of oral anti-diabetic peptide therapeutics; (2) the biological barriers for oral peptide delivery, including pH and enzyme degradation, intestinal mucosa barrier, and biodistribution barrier; (3) the delivery platforms to overcome these biological barriers. Additionally, the review will discuss the prospects in this field. The information provided in this review will serve as a valuable guide for future developments in oral anti-diabetic peptide therapeutics.
PubMed: 38799624
DOI: 10.1016/j.apsb.2024.02.019 -
Journal of Pharmaceutical Analysis May 2024The presence of -nitroso compounds, particularly -nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and... (Review)
Review
The presence of -nitroso compounds, particularly -nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of -nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.
PubMed: 38799236
DOI: 10.1016/j.jpha.2023.12.009 -
European Journal of Pharmaceutical... May 2024Bioequivalence determinations for locally acting dermatology drug products rely on assessing product sameness thru physicochemical composition and structure comparison,...
Bioequivalence determinations for locally acting dermatology drug products rely on assessing product sameness thru physicochemical composition and structure comparison, comparing the concentration of the active ingredient at the putative site of action, or comparing the clinical performance of the test (would-be generic) and reference products. Topical product action on cutaneous disease may be confounded by the action of excipients and are also subject to the inherent variability of how product may interact with the skin, including thermodynamic factors such as evaporation, spreadability, and interaction with the local environment such as heat and light and skin moisture.
PubMed: 38797441
DOI: 10.1016/j.ejps.2024.106815 -
Pharmaceutics May 2024Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of...
Automated Non-Sterile Pharmacy Compounding: A Multi-Site Study in European Hospital and Community Pharmacies with Pediatric Immediate Release Propranolol Hydrochloride Tablets.
Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is on the verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination, and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from eight countries in Europe utilized a novel automated dosing approach inspired by 3D printing for the compounding of non-sterile propranolol hydrochloride tablets. CuraBlend excipient base, a GMP-manufactured excipient base (pharma-ink) intended for automated compounding applications, was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in four different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from Phase 1 to Phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this automated and quality controlled compounding approach, extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies.
PubMed: 38794340
DOI: 10.3390/pharmaceutics16050678 -
Pharmaceutics May 2024The co-administration of curcumin and hesperetin might be beneficial in terms of neuroprotective activity; therefore, in this study, we attempted to develop a fixed-dose...
The co-administration of curcumin and hesperetin might be beneficial in terms of neuroprotective activity; therefore, in this study, we attempted to develop a fixed-dose formulation comprising these two compounds in an amorphous state. The aim of obtaining an amorphous state was to overcome the limitations of the low solubility of the active compounds. First, we assessed the possibility of using popular sweeteners (erythritol, xylitol, and sorbitol) as plasticizers to reduce the glass transition temperature of PVP K30 to prepare the polymer-excipient blends, which allowed the preparation of amorphous solid dispersions via hot-melt extrusion at a temperature below the original glass transition of PVP K30. Erythritol proved to be the superior plasticizer. Then, we focused on the development of fixed-dose amorphous solid dispersions of curcumin and hesperetin. Powder X-ray diffraction and thermal analysis confirmed the amorphous character of dispersions, whereas infrared spectroscopy helped to assess the presence of intermolecular interactions. The amorphous state of the produced dispersions was maintained for 6 months, as shown in a stability study. Pharmaceutical parameters such as dissolution rate, solubility, and in vitro permeability through artificial membranes were evaluated. The best improvement in these features was noted for the dispersion, which contained 15% of the total content of the active compounds with erythritol used as the plasticizer.
PubMed: 38794322
DOI: 10.3390/pharmaceutics16050659 -
Pharmaceutics Apr 2024Itraconazole is a drug used in veterinary medicine for the treatment of different varieties of dermatophytosis at doses between 3-5 mg/kg/day in cats. Nevertheless, in...
Itraconazole is a drug used in veterinary medicine for the treatment of different varieties of dermatophytosis at doses between 3-5 mg/kg/day in cats. Nevertheless, in Spain, it is only available in the market as a 52 mL suspension at 10 mg/mL. The lack of alternative formulations, which provide sufficient formulation to cover the treatment of large animals or allow the treatment of a group of them, can be overcome with compounding. For this purpose, it has to be considered that itraconazole is a weak base, class II compound, according to the Biopharmaceutics Classification System, that can precipitate when reaching the duodenum. The aim of this work is to develop alternative oral formulations of itraconazole for the treatment of dermatophytosis. Several oral compounds of itraconazole were prepared and compared, in terms of dissolution rate, permeability, and stability, in order to provide alternatives to the medicine commercialized. The most promising formulation contained hydroxypropyl methylcellulose and β-cyclodextrin. This combination of excipients was capable of dissolving the same concentration as the reference product and delaying the precipitation of itraconazole upon leaving the stomach. Moreover, the intestinal permeability of itraconazole was increased more than two-fold.
PubMed: 38794238
DOI: 10.3390/pharmaceutics16050576