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Scientific Data Dec 2023Self-emulsifying drug delivery systems (SEDDS) are a well-established formulation strategy for improving the oral bioavailability of poorly water-soluble drugs....
Self-emulsifying drug delivery systems (SEDDS) are a well-established formulation strategy for improving the oral bioavailability of poorly water-soluble drugs. Traditional development of these formulations relies heavily on empirical observation to assess drug and excipient compatibility, as well as to select and optimize the formulation compositions. The aim of this work was to leverage previously developed SEDDS in the literature to construct a comprehensive SEDDS dataset that can be used to gain insights and advance data-driven approaches to formulation development. A dataset comprised of 668 unique SEDDS formulations encompassing 20 poorly water-soluble drugs was curated. While there are still opportunities to enhance the quality and quantity of data on SEDDS, this research lays the groundwork to potentially simplify the SEDDS formulation development process.
Topics: Drug Delivery Systems; Emulsions; Excipients; Water
PubMed: 38123567
DOI: 10.1038/s41597-023-02812-w -
Vaccine Jul 2023Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional...
Basophil activation test (BAT) can tackle multiple mechanisms underlying acute and delayed hypersensitivity to drugs and vaccines and might complement conventional allergy diagnostics but its role in anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-related hypersensitivity is ill-defined. Therefore, 89 patients with possible hypersensitivity (56 % with delayed mucocutaneous manifestations) to anti-SARS-CoV-2 vaccines were tested with BAT for Macrogol 3350, DMG-PEG 2000, PEG 20000, polysorbate-80 and trometamol and compared to 156 subjects undergoing pre-vaccine BAT. A positive BAT was associated with delayed reaction onset (p = 0.010) and resolution (p = 0.011). BAT was more frequently positive to DMG-PEG 2000 than to other excipients in both groups (p < 0.001). DMG-PEG 2000 reactivity was less frequent in vaccine-naïve (6 %) than vaccinated subjects (35 %, p < 0.001) and associated with mRNA-1273 vaccination. DMG-PEG 2000 BAT might therefore have a diagnostic role in subjects with delayed hypersensitivity reactions. Natural immunity might be a key player in basophil activation.
Topics: Humans; Basophils; Excipients; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Hypersensitivity; Hypersensitivity, Delayed
PubMed: 37349223
DOI: 10.1016/j.vaccine.2023.06.039 -
Journal of Pharmaceutical Sciences Aug 2023Continuous direct compression (CDC) of solid oral dosage forms requires materials exhibiting acceptable flow and compression properties. The desired active...
Continuous direct compression (CDC) of solid oral dosage forms requires materials exhibiting acceptable flow and compression properties. The desired active pharmaceutical ingredient (API) powder properties can be difficult to achieve through conventional particle engineering approaches, such as particle size and habit modification during crystallization. Co-processing of API with excipients can significantly improve the powder properties to overcome these difficulties. In this manuscript, performance of a co-processed API was evaluated in a continuous feeding and blending process using GEA ConsiGma® Continuous Dosing and Blending Unit (CDB1). The co-processed theophylline was generated via a methodology in which polymer was precipitated and coated the crystalline theophylline particles resulting in nearly spherical agglomerates. A range of drug loads (1-25% w/w), flow rates (15-40 kg/h) and blender speeds (220-400 rpm) were studied. The results demonstrated that the co-processed API can be successfully fed through a loss-in-weight feeder and blended with other excipients in a high shear blender to generate tablets with acceptable content uniformity at 1-25% w/w drug loads. This study supports that using co-processed API with enhanced powder properties is a promising approach to enable continuous manufacturing for APIs with challenging properties.
Topics: Chemistry, Pharmaceutical; Excipients; Powders; Theophylline; Pharmacy; Tablets; Particle Size; Drug Compounding; Technology, Pharmaceutical
PubMed: 36462708
DOI: 10.1016/j.xphs.2022.11.023 -
Drug Research Apr 2024Four natural sweeteners (sucrose, xylitol, fructose, and isomalt) were selected to examine the influence of their qualities and amounts on the characteristics of...
Four natural sweeteners (sucrose, xylitol, fructose, and isomalt) were selected to examine the influence of their qualities and amounts on the characteristics of orodispersible films. Sodium carboxymethylcellulose (2% w/w) was utilized as the film-forming polymer and 1% w/w glycerol as a plasticizer. Films were produced through the solvent casting method, rendering them suitable for convenient application in community or hospital pharmacy settings. The physicochemical and optical properties of the films were analyzed, and Fourier-transform infrared analysis was carried out. All films exhibited acceptable disintegration time, uniformity of mass, thickness, and optical characteristics, with significant dependence (p<0.05) on both sweetener type and quantity. Disintegration time varied based on the employed method, as well as the characteristics and amount of sweetener. Additionally, all films maintained pH values within the oral cavity range, suggesting no potential irritancy upon administration. Fourier-transform infrared analysis confirmed the formation of the film and demonstrated compatibility between its components.
Topics: Sweetening Agents; Chemistry, Pharmaceutical; Solubility; Administration, Oral; Solvents; Excipients
PubMed: 38508227
DOI: 10.1055/a-2266-2522 -
Journal of Pharmaceutical and... Sep 2023Controlling monoclonal antibody aggregation at the upstream stage itself can significantly reduce the burden on downstream processing and can improve the process yield.... (Review)
Review
Controlling monoclonal antibody aggregation during cell culture using medium additives facilitated by the monitoring of aggregation in cell culture matrix using size exclusion chromatography.
Controlling monoclonal antibody aggregation at the upstream stage itself can significantly reduce the burden on downstream processing and can improve the process yield. Hence, we have investigated the use of sugar osmolytes (glucose, mannose, sucrose and maltose) and formulation excipients (mannitol, polysorbate 20 and polysorbate 80) as medium additives to reduce protein aggregation during cell culture. Aggregate content in cell culture samples was estimated using a high-resolution size-exclusion chromatography technique, which efficiently resolved the antibody monomer and aggregates in the cell culture matrix i.e., without purification. Glucose, mannose, maltose and the polysorbates effectively reduced the mean aggregate content over the course of the culture. Sugar-based additives exhibited a higher degree of variation during aggregate quantitation as compared to polysorbate additives, rendering the latter a preferred additive. Therefore, this study demonstrated the potential of sugar osmolytes and formulation excipients as media additives during cell culture to reduce aggregate formation, without negatively impacting cell growth and antibody production, facilitated by the monitoring of aggregate content in cell culture samples without purification.
Topics: Antibodies, Monoclonal; Excipients; Maltose; Mannose; Polysorbates; Chromatography, Gel; Cell Culture Techniques; Glucose
PubMed: 37467528
DOI: 10.1016/j.jpba.2023.115575 -
AAPS PharmSciTech Apr 2024Although biopharmaceuticals constitute around 10% of the drug landscape, eight of the ten top-selling products were biopharmaceuticals in 2023. This study did a... (Review)
Review
Although biopharmaceuticals constitute around 10% of the drug landscape, eight of the ten top-selling products were biopharmaceuticals in 2023. This study did a comprehensive analysis of the FDA's Purple Book database. Firstly, our research uncovered market trends and provided insights into biologics distributions. According to the investigation, although biotechnology has advanced and legislative shifts have made the approval process faster, there are still challenges to overcome, such as molecular instability and formulation design. Moreover, our research comprehensively analyzed biological formulations, pointing out significant strategies regarding administration routes, dosage forms, product packaging, and excipients. In conjunction with biologics, the widespread integration of innovative delivery strategies will be implemented to confront the evolving challenges in healthcare and meet an expanding array of treatment needs.
Topics: United States; Pharmaceutical Preparations; Excipients; Biological Products; United States Food and Drug Administration; Drug Approval
PubMed: 38637407
DOI: 10.1208/s12249-024-02802-0 -
Biomaterials Science Oct 2023Periodontal dressing is a surgical dressing applied to oral wounds after periodontal surgery. Currently, all commercially available setting periodontal dressings are...
Periodontal dressing is a surgical dressing applied to oral wounds after periodontal surgery. Currently, all commercially available setting periodontal dressings are stiff, uncomfortable, with poor aesthetics, and need to be removed at the patient's follow-up visit, which may cause secondary damage. A periodontal dressing with soft texture, biodegradable properties, and that could balance both comfort and aesthetics is urgently desired. Hence, non-setting and degradable dressings were developed using sodium carboxymethyl cellulose, Eudragit S 100 and povidone K30, which were compared with the commercial degradable dressing Reso-pac®. The mucosal adhesion of the dressings was evaluated by lap shear tests, which indicated adequate adhesion. The swelling rates of the dressings were approximately half that of Reso-pac®, which led to less saliva adsorption and better dimensional stability. The dressings also exhibited satisfactory biocompatibility according to the results of CCK-8, Live/Dead staining, hemolysis, and subcutaneous implantation assays. Moreover, the dressing promoted the healing of full-thickness mucosal wounds in the palatal gingivae of SD rats and contributed to better therapeutic effect than Reso-pac®. Considering the multiple advantages and the pure pharmaceutical excipient formula, we anticipate that this dressing could be a promising product and may enter clinical practice in the near future.
PubMed: 37724849
DOI: 10.1039/d3bm01314f -
The Analyst Feb 2024Pharmaceutical polymers and excipients represent interesting but often overlooked chemical classes in clinical exposure and bioanalytical research. These chemicals may...
High-abundance peaks and peak clusters associate with pharmaceutical polymers and excipients in urinary untargeted clinical metabolomics data: exploration of their origin and possible impact on label-free quantification.
Pharmaceutical polymers and excipients represent interesting but often overlooked chemical classes in clinical exposure and bioanalytical research. These chemicals may cause hypersensitivity reactions, they can be useful to confirm exposure to pharmaceuticals, and they may pose bioanalytical challenges, including ion suppression in liquid chromatography-mass spectrometry (LC-MS-)based workflows. In this work, we assessed these chemicals in light of a rather surprising finding presented in two previously published studies, namely that usage of cyclosporine A, an immunosuppressive drug which is known to be cleared through excretion in the bile, explained the largest amount of variance in principal component analysis of urinary LC-SWATH/MS small-molecule profiling data. Specifically, we examined the freely-accessible 24-hour urine metabolomics data of 570 kidney transplant recipients included in the TransplantLines Biobank and Cohort Study (NCT03272841). These data unveiled thousands of high-abundance polymer peaks in some samples, which were associated with the use of the macrogol (, polyethylene glycol) 3350 oral laxative agent. In addition, we found multiple clusters of high-abundance peaks which were linked to the exposure to two pharmaceutical excipients, namely short-chain polyethylene glycol (molecular weight <1000 Da) and polyethoxylated castor oil (also known as Kolliphor® EL or Cremophor® EL). Respectively, these excipients are used in temazepam capsules and cyclosporine A capsules, and the latter provides a plausible explanation for the rather surprising finding that instigated our work. Moreover, such explanation and our findings in general put emphasis on taking into consideration these and other pharmaceutical polymers and excipients when exploring, processing, and interpreting clinical small-molecule profiling data.
Topics: Humans; Excipients; Cyclosporine; Polymers; Cohort Studies; Polyethylene Glycols; Metabolomics
PubMed: 38251754
DOI: 10.1039/d3an01874a -
BioMed Research International 2023Binders are ingredients used in tablet granulation process for tablet cohesiveness which confirms that the tablet remains intact after compression. Natural gums have...
Binders are ingredients used in tablet granulation process for tablet cohesiveness which confirms that the tablet remains intact after compression. Natural gums have been employed as disintegrants, emulsifying agents, suspending agents, and binders in tablets. Even though gum is claimed as a possible pharmaceutical excipient by some phytochemical studies, literature is scanty on its efficacy as a tablet binder. The purpose of this study was to isolate, characterize, and comparatively evaluate gum as a potential binder in tablet formulation. Gum was extracted from tree, characterized for physicochemical properties, and applied as a binder in paracetamol granule and tablet formulation. Granules were prepared using 4%, 6%, 8%, and 10% w/w concentration of the gum and standard binders (polyvinylpyrrolidone K-30 and Starch1500) by wet granulation. The formulated tablets were then evaluated for tablet quality parameters, and comparison between the test and standard binders was done by ANOVA. The dried crude gum yielded 50.63% (w/w) of a brownish yellow purified gum. The angle of repose, Carr's index, and the Hausner ratio all complied with the pharmacopoeial recommendations. The gum is compatible with the model drug, paracetamol. The paracetamol granules prepared with gum binder demonstrated an optimum size range and size distribution with substantial flow and compressibility properties. gum binder demonstrated significantly higher disintegration time and strength properties than that of similar concentrations of Starch1500 but lower than polyvinylpyrrolidone ( < 0.05). gum has better binding properties than starch but lower than polyvinylpyrrolidone. Hence, gum can be used as an alternative tablet binder in tablet manufacturing.
Topics: Excipients; Ficus; Acetaminophen; Povidone; Starch; Tablets
PubMed: 37593524
DOI: 10.1155/2023/8852784 -
Human Vaccines & Immunotherapeutics Dec 2023Coronavirus (COVID-19) vaccines have proved to be effective in the pandemic response but can cause adverse events such as delayed hypersensitivity reactions (DHRs)....
Coronavirus (COVID-19) vaccines have proved to be effective in the pandemic response but can cause adverse events such as delayed hypersensitivity reactions (DHRs). Delayed-reading intradermal tests (IDT) to vaccines are limited by false-positive results and may reflect a cell-mediated rather than IgE-mediated immune response. Lymphocyte transformation test (LTT), which has been utilized in the diagnosis of drug allergy, may be helpful in suspected COVID-19 vaccine and/or its excipient-related DHRs. To investigate the use of LTT in two suspected cases of COVID-19 vaccine-induced DHRs, two patients with suspected DHRs to COVID-19 vaccination were tested by delayed-reading IDT and LTT against vaccines and their excipients. A 47-year-old man developed acute mixed-pattern hepatitis after the second dose of ChAdOx1 vaccine. LTT performed at 2 months post-vaccination revealed reactivity to the ChAdOx1 vaccine, polysorbate 80 and mildly to PEG 2050 but not BNT162b2 vaccine. Delayed-reading IDT returned negative to both vaccines and excipients. He tolerated BNT162b2 vaccination with no adverse events. A 36-year-old woman presented with subacute morbilliform eruption and hepatitis after the first dose of BNT162b2 vaccine. LTT performed 3 months later revealed reactivity to the BNT162b2 but not PEG 2050. Repeat LTT following subsequent natural Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) infection revealed reactivity to ChAdOx1 and NVX-CoV2373 vaccines but not polysorbate 80. Delayed-reading IDT remained negative. She proceeded with NVX-CoV2373 vaccination with no symptom recurrence. LTT may be a useful tool in suspected COVID-19 vaccine-related DHRs. Further evaluation with a larger patient cohort is required.
Topics: Adult; Female; Humans; Male; Middle Aged; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Excipients; Hypersensitivity, Delayed; Lymphocyte Activation; Polysorbates; SARS-CoV-2; Vaccination
PubMed: 36912718
DOI: 10.1080/21645515.2023.2182527