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Molecules (Basel, Switzerland) Sep 2023The ecotoxicological impact of pharmaceuticals has received considerable attention, primarily focusing on active pharmaceutical ingredients (APIs) while largely...
The ecotoxicological impact of pharmaceuticals has received considerable attention, primarily focusing on active pharmaceutical ingredients (APIs) while largely neglecting the potential hazards posed by pharmaceutical excipients. Therefore, we analyzed the ecotoxicity of 16 commonly used pharmaceutical excipients, as well as 26 API-excipient and excipient-excipient mixtures utilizing the Microtox test. In this way, we assessed the potential risks that pharmaceutical excipients, generally considered safe, might pose to the aquatic environment. We investigated both their individual ecotoxicity and their interactions with tablet ingredients using concentration addition (CA) and independent action (IA) models to shed light on the often-overlooked ecotoxicological consequences of these substances. The CA model gave a more accurate prediction of toxicity and should be recommended for modeling the toxicity of combinations of drugs with different effects. A challenge when studying the ecotoxicological impact of some pharmaceutical excipients is their poor water solubility, which hinders the use of standard aquatic ecotoxicity testing techniques. Therefore, we used a modification of the Microtox Basic Solid Phase protocol developed for poorly soluble substances. The results obtained suggest the high toxicity of some excipients, i.e., SLS and meglumine, and confirm the occurrence of interactions between APIs and excipients. Through this research, we hope to foster a better understanding of the ecological impact of pharmaceutical excipients, prompting the development of risk assessment strategies within the pharmaceutical industry.
Topics: Excipients; Risk Assessment; Environment; Drug Industry; Pharmaceutical Preparations
PubMed: 37764366
DOI: 10.3390/molecules28186590 -
International Journal of Environmental... Dec 2022Excipients are used as vehicles for topical treatments; however, there are not many studies that evaluate the impact of different excipients themselves. The aim of this...
Excipients are used as vehicles for topical treatments; however, there are not many studies that evaluate the impact of different excipients themselves. The aim of this research is to assess skin homeostasis changes in healthy individuals after using water/oil (W/O), oil/water (O/W), Beeler base, foam and Vaseline excipients. A within-person randomized trial was conducted that included healthy individuals without previous skin diseases. Skin barrier function parameters, including stratum corneum hydration (SCH), transepidermal water loss (TEWL), pH, temperature, erythema, melanin and elasticity (R0, R2, R5 and R7), were measured on the volar forearm before and after using each excipient. Sixty participants were included in the study, with a mean age of 32 years. After applying w/o excipient erythema decreased by 25 AU, ( < 0.001) and elasticity increased by 6%. After using the o/w excipient, erythema decreased by 39.36 AU ( < 0.001) and SCH increased by 6.85 AU ( = 0.009). When applying the Beeler excipient, erythema decreased by 41.23 AU ( < 0.001) and SCH increased by 15.92 AU ( < 0.001). Foam and Vaseline decreased TEWL and erythema. Excipients have a different impact on skin barrier function. Knowing the effect of excipients on the skin could help to develop new topical treatments and help specialists to choose the best excipient according to the pathology.
Topics: Humans; Adult; Excipients; Skin; Petrolatum; Administration, Topical; Erythema
PubMed: 36554558
DOI: 10.3390/ijerph192416678 -
Acta Poloniae Pharmaceutica 2012The objective of this study was to extend the GI residence time of the dosage form and to control the release of domperidone using directly compressible sustained...
The objective of this study was to extend the GI residence time of the dosage form and to control the release of domperidone using directly compressible sustained release mucoadhesive matrix (SRMM) tablets. A 2-factor centre composite design (CCD) was employed to study the influence of independent variables like gum ghatti (GG) (X1) and hydroxylpropylmethyl cellulose K 15M (HPMC K 15M) (X2) on dependent variable like mucoadhesive strength, tensile strength, release exponent (n), t50 (time for 50% drug release), rel(10 h) (release after 10 h) and rel(18 h) (release after 18 h). Tablets were prepared by direct compression technology and evaluated for tablet parametric test (drug assay, diameter, thickness, hardness and tensile strength), mucoadhesive strength (using texture analyzer) and in vitro drug release studies. The tensile strength and mucoadhesive strength were found to be increased from 0.665 +/- 0.1 to 1.591 +/- 0.1 MN/cm2 (Z1 to Z9) and 10.789 +/- 0.985 to 50.924 +/- 1.150 N (Z1 to Z9), respectively. The release kinetics follows first order and Hixson Crowell equation indicating drug release following combination of diffusion and erosion. The n varies between 0.834 and 1.273, indicating release mechanism shifts from non fickian (anomalous release) to super case II, which depict that drug follows multiple drug release mechanism. The t50 time was found to increase from 5 +/- 0.12 to 11.4 +/- 0.14 h (Z1 to Z9) and release after 10 and 18 h decreases with increasing concentration of both polymers concluding with release controlling potential of polymers. The accelerated stability studies were performed on optimized formulation as per ICH guideline and the result showed that there was no significant change in tensile strength, mucoadhesive strength and drug assay.
Topics: Adhesiveness; Animals; Antiemetics; Chemistry, Pharmaceutical; Delayed-Action Preparations; Domperidone; Dopamine Antagonists; Drug Compounding; Excipients; Gastric Mucosa; Hardness; Hypromellose Derivatives; Kinetics; Methylcellulose; Models, Chemical; Plant Gums; Solubility; Swine; Tablets; Technology, Pharmaceutical; Tensile Strength
PubMed: 22876617
DOI: No ID Found -
Molecules (Basel, Switzerland) Oct 2023It is widely recognized that many active pharmaceutical ingredients (APIs) have a disagreeable taste that affects patient acceptability, particularly in children.... (Review)
Review
It is widely recognized that many active pharmaceutical ingredients (APIs) have a disagreeable taste that affects patient acceptability, particularly in children. Consequently, developing dosage forms with a masked taste has attracted a lot of interest. The application of cyclodextrins as pharmaceutical excipients is highly appreciated and well established, including their roles as drug delivery systems, solubilizers and absorption promoters, agents that improve drug stability, or even APIs. The first work describing the application of the taste-masking properties of CDs as pharmaceutical excipients was published in 2001. Since then, numerous studies have shown that these cyclic oligosaccharides can be effectively used for such purposes. Therefore, the aim of this review is to provide insight into studies in this area. To achieve this aim, a systematic evaluation was conducted, which resulted in the selection of 67 works representing both successful and unsuccessful works describing the application of CDs as taste-masking excipients. Particular attention has been given to the methods of evaluation of the taste-masking properties and the factors affecting the outcomes, such as the choice of the proper cyclodextrin or guest-host molar ratio. The conclusions of this review reveal that the application of CDs is not straightforward; nevertheless, this solution can be an effective, safe, and inexpensive method of taste masking for pharmaceutical purposes.
Topics: Child; Humans; Pharmaceutical Preparations; Excipients; Cyclodextrins; Taste; Chemistry, Pharmaceutical; Solubility
PubMed: 37836807
DOI: 10.3390/molecules28196964 -
Molecular Pharmaceutics May 2023Protein-based therapeutics typically require high concentrations of the active protein, which can lead to protein aggregation and high solution viscosity. Such solution...
Protein-based therapeutics typically require high concentrations of the active protein, which can lead to protein aggregation and high solution viscosity. Such solution behaviors can limit the stability, bioavailability, and manufacturability of protein-based therapeutics and are directly influenced by the charge of a protein. Protein charge is a system property affected by its environment, including the buffer composition, pH, and temperature. Thus, the charge calculated by summing the charges of each residue in a protein, as is commonly done in computational methods, may significantly differ from the effective charge of the protein as these calculations do not account for contributions from bound ions. Here, we present an extension of the structure-based approach termed site identification by ligand competitive saturation-biologics (SILCS-Biologics) to predict the effective charge of proteins. The SILCS-Biologics approach was applied on a range of protein targets in different salt environments for which membrane-confined electrophoresis-determined charges were previously reported. SILCS-Biologics maps the 3D distribution and predicted occupancy of ions, buffer molecules, and excipient molecules bound to the protein surface in a given salt environment. Using this information, the effective charge of the protein is predicted such that the concentrations of the ions and the presence of excipients or buffers are accounted for. Additionally, SILCS-Biologics also produces 3D structures of the binding sites of ions on the proteins, which enable further analyses such as the characterization of protein surface charge distribution and dipole moments in different environments. Notable is the capability of the method to account for competition between salts, excipients, and buffers on the calculated electrostatic properties in different protein formulations. Our study demonstrates the ability of the SILCS-Biologics approach to predict the effective charge of proteins and its applicability in uncovering protein-ion interactions and their contributions to protein solubility and function.
Topics: Biological Products; Ligands; Excipients; Proteins; Binding Sites
PubMed: 37017675
DOI: 10.1021/acs.molpharmaceut.3c00064 -
International Journal of Pharmaceutics Jun 2022Starch-based tablets with tailored releases were prepared by 3D printing using a hydrophobic drug. The importance of the origin of the excipient in the inks and tablets...
Starch-based tablets with tailored releases were prepared by 3D printing using a hydrophobic drug. The importance of the origin of the excipient in the inks and tablets was analyzed. Besides, the effect of the geometry of the tablet on the drug release profile was also evaluated. The rheological properties of the inks was influenced by the botanic origin of the starch. Consequently, tablets presented different microporous structure and particular compression and swelling behaviors. Normal maize starch showed a non-well-defined porous morphology, not being able to form a stable structure whereas, waxy maize and potato starches exhibited a well-defined porous structure and were both able to maintain their integrity after long time immersion. Finally, tablets combining different starches and geometries were printed tailoring the drug release from 10 min to 6 h and designing two-steps profiles. The applicability of the developed 3D printed drug release systems in personalized therapies was demonstrated.
Topics: Drug Liberation; Excipients; Kinetics; Printing, Three-Dimensional; Starch; Tablets; Technology, Pharmaceutical
PubMed: 35636631
DOI: 10.1016/j.ijpharm.2022.121872 -
Analytical and Bioanalytical Chemistry Feb 2023Monitoring the protein concentration and buffer composition during the Ultrafiltration/Diafiltration (UF/DF) step enables the further automation of biopharmaceutical...
Monitoring the protein concentration and buffer composition during the Ultrafiltration/Diafiltration (UF/DF) step enables the further automation of biopharmaceutical production and supports Real-time Release Testing (RTRT). Previously, in-line Ultraviolet (UV) and Infrared (IR) measurements have been used to successfully monitor the protein concentration over a large range. The progress of the diafiltration step has been monitored with density measurements and Infrared Spectroscopy (IR). Raman spectroscopy is capable of measuring both the protein and excipient concentration while being more robust and suitable for production measurements in comparison to Infrared Spectroscopy (IR). Regardless of the spectroscopic sensor used, the low concentration of excipients poses a challenge for the sensors. By combining sensor measurements with a semi-mechanistic model through an Extended Kalman Filter (EKF), the sensitivity to determine the progress of the diafiltration can be improved. In this study, Raman measurements are combined with an EKF for three case studies. The advantages of Kalman-filtered Raman measurements for excipient monitoring are shown in comparison to density measurements. Furthermore, Raman measurements showed a higher measurement speed in comparison to Variable Pathlength (VP) UV measurement at the trade-off of a slightly worse prediction accuracy for the protein concentration. However, the Raman-based protein concentration measurements relied mostly on an increase in the background signal during the process and not on proteinaceous features, which could pose a challenge due to the potential influence of batch variability on the background signal. Overall, the combination of Raman spectroscopy and EKF is a promising tool for monitoring the UF/DF step and enables process automation by using adaptive process control.
Topics: Excipients; Ultrafiltration; Proteins; Spectrum Analysis, Raman; Spectrophotometry, Infrared
PubMed: 36651972
DOI: 10.1007/s00216-022-04477-7 -
European Journal of Pharmaceutics and... Nov 2022In the current study, the concept of multiparticulate drug delivery systems (MDDS) was applied to tablets intended for the amorphisation of supersaturated granular ASDs...
In the current study, the concept of multiparticulate drug delivery systems (MDDS) was applied to tablets intended for the amorphisation of supersaturated granular ASDs in situ, i.e. amorphisation within the final dosage form by microwave irradiation. The MDDS concept was hypothesised to ensure geometric and structural stability of the dosage form and to improve the in vitro disintegration and dissolution characteristics. Granules were prepared in two sizes (small and large) containing the crystalline drug celecoxib (CCX) and polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA) at a 50 % w/w drug load as well as sodium dihydrogen phosphate monohydrate as the microwave absorbing excipient. The granules were subsequently embedded in an extra-granular tablet phase composed of either the filler microcrystalline cellulose (MCC) or mannitol (MAN), as well as the disintegrant crospovidone and the lubricant magnesium stearate. The tensile strength and disintegration time were investigated prior to and after 10 min of microwave irradiation (800 and 1000 W) and the formed ASDs were characterised by X-ray powder diffraction and modulated differential scanning calorimetry. Additionally, the internal structure was elucidated by X-ray micro-Computed Tomography (XµCT) and, finally, the dissolution performance of selected tablets was investigated. The MDDS tablets displayed no geometrical changes after microwave irradiation, however, the tensile strength and disintegration time generally increased. Complete amorphisation of CCX was achieved only for the MCC-based tablets at a power input of 1000 W, while MAN-based tablets displayed partial amorphisation independent of power input. The complete amorphisation of CCX was associated with the fusion of individual ASD granules within the tablets, which negatively impacted the subsequent disintegration and dissolution performance. For these tablets, supersaturation was only observed after 60 min. On the other hand, the partially amorphised MDDS tablets displayed complete disintegration during the dissolution experiments, resulting in a fast onset of supersaturation within 5 min and an approx. 3.5-fold degree of supersaturation within the experimental timeframe (3 h). Overall, the MDDS concept was shown to potentially be a feasible dosage form for in situ amorphisation, however, there is still room for improvement to obtain a both fully amorphous and disintegrating system.
Topics: Humans; Chemistry, Pharmaceutical; X-Ray Microtomography; Tablets; Povidone; Excipients; Celecoxib; Mannitol; Drug Delivery Systems; Solubility
PubMed: 36191869
DOI: 10.1016/j.ejpb.2022.09.021 -
International Journal of Pharmaceutics Jan 2016
Topics: Excipients; Glycerol; Humans; Ursodeoxycholic Acid
PubMed: 26611667
DOI: 10.1016/j.ijpharm.2015.11.006 -
BioMed Research International 2021The objective of the study was to investigate the suitability of the (PO) husk as a pharmaceutical excipient. Various phytoconstituents of the husk were determined...
The objective of the study was to investigate the suitability of the (PO) husk as a pharmaceutical excipient. Various phytoconstituents of the husk were determined according to the standard test procedures. The husk was evaluated for various pharmaceutical parameters related to flow, swelling index, and compressibility index. Orodispersible tablets (ODTs) were prepared, containing different concentrations (2.5, 3, 5, 7.5, 10, and 15% /) of the husk. Before compression, all the formulations were evaluated for their flow. Compressed ODTs were evaluated for physical characteristics (physical appearance, weight and weight variation, thickness, and moisture content), mechanical strength (crushing strength, specific crushing strength, tensile strength, and friability), disintegration behavior (disintegration time and oral disintegration time), drug content, and in vitro drug release. Phytochemical evaluation of the husk confirmed the presence of various phytoconstituents like alkaloids, tannins, glycosides, saponins, flavonoids, and phenols. SEM photograph of the husk showed that it has a fibrous structure, with a porous and rough surface. The husk had a high swelling index (380%) which decreased by pulverization (310%). Precompression evaluation of the powder blend for all the formulations of ODTs showed good flow properties, indicating that the husk improved the rheological characteristics of the powder blend. Compressed ODTs had good mechanical strength, and their friability was within the official limits (<1%). Best disintegration was observed with formulation F-6 containing 10% / of the husk. It is concluded that the husk can be used as a disintegrant in the formulation of ODTs.
Topics: Chemistry, Pharmaceutical; Compressive Strength; Dietary Fiber; Drug Liberation; Excipients; Microscopy, Electron, Scanning; Plantago; Porosity; Powders; Saponins; Stress, Mechanical; Tablets; Tensile Strength; Time Factors; X-Ray Diffraction
PubMed: 34235217
DOI: 10.1155/2021/5538075