Excipients Used in Pharmaceutical Dosage Forms

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 21108

Special Issue Editors


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Guest Editor
Institute Charles Gerhardt Montpellier (ICGM), University of Montpellier, CNRS, ENSCM, 34000 Montpellier, France
Interests: pharmaceutical excipients; oral drug delivery; direct compression; co-processing; 3D printed medicines for oral drug de-livery; development of novel high-performance excipients for drug formulation
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Pharmacy, Nîmes University Hospital, 30900 Nimes, France
Interests: pharmaceutical development; solid form; pediatric; pharmaceutical technology

Special Issue Information

Dear Colleagues,

Pharmaceutical excipients play a central role in the drug development process, the formulation of stable dosage forms and their administration. They are often the main components of any pharmaceutical’s formulation and crucial for its safe and effective use.

Over the last two decades, the development of pharmaceutical excipients has gained importance and a high growth rate due their demand as appropriate carriers or formulations for new active molecules, solubility-enhancing excipients, formulations providing a controlled therapeutic window, improved bioavailability or greater specificity, and non-toxic administration strategies for certain treatments such as chemotherapeutics. Considering the ongoing developments in the field of advanced pharmaceutical formulations, this Special Issue aims to gather and review the latest advances in the development of excipients and formulation strategies used to improve oral drug protection, absorption and delivery. Additionally, attention will also be given to advances in pediatric and geriatric formulations and emerging personalized treatments, such as 3D printing. 

Dr. Noelia Sanchez-Ballester
Dr. Ian Soulairol
Guest Editors

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Keywords

  • pharmaceutical excipient
  • oral drug delivery
  • excipients development
  • formulations
  • enhanced drug performance

Published Papers (9 papers)

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Research

13 pages, 3196 KiB  
Article
Utilization and Evaluation of Rice Bran and Rice Bran Wax as a Tablet Lubricant
by Ornanong S. Kittipongpatana, Karnkamol Trisopon, Phanphen Wattanaarsakit and Nisit Kittipongpatana
Pharmaceutics 2024, 16(3), 428; https://doi.org/10.3390/pharmaceutics16030428 - 20 Mar 2024
Viewed by 802
Abstract
The rice bran and rice bran wax of the KJ CMU107 rice strain were investigated as potential tablet lubricants in a directly compressed tablet formulation. Stabilized full-fatted rice bran (sFFRB), stabilized defatted rice bran (sDFRB), and rice bran wax (RBW) extracted and purified [...] Read more.
The rice bran and rice bran wax of the KJ CMU107 rice strain were investigated as potential tablet lubricants in a directly compressed tablet formulation. Stabilized full-fatted rice bran (sFFRB), stabilized defatted rice bran (sDFRB), and rice bran wax (RBW) extracted and purified from crude rice bran oil (cRBO) were tested. Two commercial lubricants, including magnesium stearate (MGS) and hydrogenated cottonseed oil (HVO), were employed as the standards in the formulated mixtures, which contained spray-dried rice starch (SDRS) as a diluent. The tableting was carried out for each formulation, and the obtained tablets were physically and mechanically evaluated. Among the parameters investigated were the general appearance, ejection force, weight variation, hardness, friability, and disintegration time. The powder flow was also determined for each formulation. The results showed that the tablet ejection forces for all the lubricated formulations (58–259 N) were significantly lower than that of the non-lubricated control formulation (349 N). The use of sFFRB as a lubricant at 0.5–2.0% w/w could lower the ejection force up to 78%, but the hardness reduced so drastically that the formulations failed the friability test due to the chipping of the tablets’ edges. Moreover, sDFRB performed significantly better as the use at 0.5–1.0% w/w in the formulation helped to lower the ejection forces by up to 80% while maintaining the changes in the tablet hardness within 10%. RBW functioned effectively as a tablet lubricant at a concentration of 0.5% w/w, yielding tablets with good strength comparable to standard HVO lubricant while helping to reduce the ejection force by 82%. In formulations with good lubrication, i.e., friability < 1%, the powder flow was improved, and the tablet disintegration times were within the same range as the control and HVO formulations. In conclusion, sDFRB displayed a lubricant property at concentrations between 0.5 and 1.0% w/w, with slightly negative effects on the tablet hardness. RBW from KJ CMU107 rice was an effective tablet lubricant at 0.5% w/w, with no effect on tablet hardness. Both materials can be further developed for use as commercial lubricants in direct compression. Full article
(This article belongs to the Special Issue Excipients Used in Pharmaceutical Dosage Forms)
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27 pages, 351 KiB  
Article
Potentially Harmful Excipients: State of the Art for Oral Liquid Forms Used in Neonatology and Pediatrics Units
by Marianne Bobillot, Violaine Delannoy, Alexandre Trouillard, Jean Marie Kinowski, Noelia Maria Sanchez-Ballester and Ian Soulairol
Pharmaceutics 2024, 16(1), 119; https://doi.org/10.3390/pharmaceutics16010119 - 17 Jan 2024
Viewed by 1933
Abstract
The pediatric population exhibits an important age-dependent heterogeneity in pharmacokinetics and pharmacodynamics parameters, resulting in differences in drug efficacy and toxicity compared to the adult population, particularly for neonates. Toxicity and efficacy divergences have been studied for active molecules, but the impact on [...] Read more.
The pediatric population exhibits an important age-dependent heterogeneity in pharmacokinetics and pharmacodynamics parameters, resulting in differences in drug efficacy and toxicity compared to the adult population, particularly for neonates. Toxicity and efficacy divergences have been studied for active molecules, but the impact on the pharmacological parameters of excipients remains less well known. To fill this lack of knowledge, several initiatives have been started to gather information on the specific toxicity of excipients, such as the KIDS list or the STEP database. In order to contribute to this much-needed action, in this work, a compilation of the 219 formulations of oral liquid forms prescribed in pediatrics and neonatology units was established based on the summary of product characteristics. Then, for excipients found in more than 10% of the analyzed formulations, a review of their toxicity data was carried out using the STEP database. Finally, for a selection of 10 frequently used liquid forms, the amounts of excipients administered daily were calculated based on the recommended posology in the Summary of Product Characteristics (SPC) and compared with the recommended daily limits proposed by the European Medicine Agency. Pediatrics-adapted formulations are still rare, and it is not always possible to find safe alternatives to drugs containing excipients of interest. Full article
(This article belongs to the Special Issue Excipients Used in Pharmaceutical Dosage Forms)
17 pages, 5102 KiB  
Article
Three-Dimensional-Printed Oral Films Based on LCD: Influence Factors of the Film Printability and Received Qualities
by Tingfeng Xu, Huijie Li, Yi Xia, Sheng Ding, Qingliang Yang and Gensheng Yang
Pharmaceutics 2023, 15(3), 758; https://doi.org/10.3390/pharmaceutics15030758 - 24 Feb 2023
Cited by 2 | Viewed by 1624
Abstract
As an oral mucosal drug delivery system, oral films have been of wide concern in recent years because of their advantages such as rapid absorption, being easy to swallow and avoiding the first-pass effect common for mucoadhesive oral films. However, the currently utilized [...] Read more.
As an oral mucosal drug delivery system, oral films have been of wide concern in recent years because of their advantages such as rapid absorption, being easy to swallow and avoiding the first-pass effect common for mucoadhesive oral films. However, the currently utilized manufacturing approaches including solvent casting have many limitations, such as solvent residue and difficulties in drying, and are not suitable for personalized customization. To solve these problems, the present study utilizes liquid crystal display (LCD), a photopolymerization-based 3D printing technique, to fabricate mucoadhesive films for oral mucosal drug delivery. The designed printing formulation includes PEGDA as the printing resin, TPO as the photoinitiator, tartrazine as the photoabsorber, PEG 300 as the additive and HPMC as the bioadhesive material. The influence of printing formulation and printing parameters on the printing formability of the oral films were elucidated in depth, and the results suggested that PEG 300 in the formulation not only provided the necessary flexibility of the printed oral films, but also improved drug release rate due to its role as pore former in the produced films. The presence of HPMC could greatly improve the adhesiveness of the 3D-printed oral films, but excessive HPMC increased the viscosity of the printing resin solution, which could strongly hinder the photo-crosslinking reaction and reduce printability. Based on the optimized printing formulation and printing parameters, the bilayer oral films containing a backing layer and an adhesive layer were successfully printed with stable dimensions, adequate mechanical properties, strong adhesion ability, desirable drug release and efficient in vivo therapeutic efficacy. All these results indicated that an LCD-based 3D printing technique is a promising alternative to precisely fabricate oral films for personalized medicine. Full article
(This article belongs to the Special Issue Excipients Used in Pharmaceutical Dosage Forms)
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15 pages, 6423 KiB  
Article
Tablet Disintegratability: Sensitivity of Superdisintegrants to Temperature and Compaction Pressure
by Audrey Yi Zheng, Paul Wan Sia Heng and Lai Wah Chan
Pharmaceutics 2022, 14(12), 2725; https://doi.org/10.3390/pharmaceutics14122725 - 6 Dec 2022
Cited by 4 | Viewed by 4730
Abstract
Tablet disintegration is an important pre-requisite for drug dissolution and absorption. The disintegration test is typically conducted at 37 °C, but the intragastric temperature may vary due to meals or fever. This study investigated the effects of temperature and compaction pressure on tablet [...] Read more.
Tablet disintegration is an important pre-requisite for drug dissolution and absorption. The disintegration test is typically conducted at 37 °C, but the intragastric temperature may vary due to meals or fever. This study investigated the effects of temperature and compaction pressure on tablet disintegratability to gain deeper insights into superdisintegrant sensitivity and function. Tablets with either sodium starch glycolate or crospovidone as disintegrant were prepared at various compaction pressures and subjected to the disintegration test using different medium temperatures. Preheating of tablets was also employed to establish instant temperature equilibrium between the tablet and the disintegration medium. Liquid penetration and disintegration were faster as the medium temperature increased or compaction pressure decreased. Swelling or strain recovery disintegrants exhibited similar sensitivity to variations in the medium temperature. Preheating of the tablets resulted in slower disintegration, but this effect was reversible upon cooling, hence the slower disintegration was unlikely to be attributed to changes in the disintegrant physical state. The temperature difference between the tablet and the disintegration medium likely affected the rate of fluid flow into tablets and influenced disintegration. Understanding disintegrant temperature sensitivity would help to avoid unacceptable fluctuations in disintegration due to temperature variations. The temperature difference effect could also be harnessed to boost disintegrant performance. Full article
(This article belongs to the Special Issue Excipients Used in Pharmaceutical Dosage Forms)
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25 pages, 4048 KiB  
Article
Control Strategy for Excipient Variability in the Quality by Design Approach Using Statistical Analysis and Predictive Model: Effect of Microcrystalline Cellulose Variability on Design Space
by Ji Yeon Kim and Du Hyung Choi
Pharmaceutics 2022, 14(11), 2416; https://doi.org/10.3390/pharmaceutics14112416 - 8 Nov 2022
Cited by 2 | Viewed by 2678
Abstract
Although various quality by design (QbD) approaches have been used to establish a design space to obtain robust drug formulation and process parameters, the effect of excipient variability on the design space and drug product quality is unclear. In this study, the effect [...] Read more.
Although various quality by design (QbD) approaches have been used to establish a design space to obtain robust drug formulation and process parameters, the effect of excipient variability on the design space and drug product quality is unclear. In this study, the effect of microcrystalline cellulose (MCC) variability on drug product quality was examined using a design space for immediate-release tablets of amlodipine besylate. MCC variability was assessed by altering the manufacturer and grade. The formulation was developed by employing the QbD approach, which was optimized using a D-optimal mixture design. Using 36 different MCCs, the effect of MCC variability on the design space was assessed. The design space was shifted by different manufacturers and grades of MCC, which resulted in associations between the physicochemical properties of MCC and critical quality attributes (CQAs). The correlation between the physicochemical properties of MCCs and CQAs was assessed through a statistical analysis. A predictive model correlating the physicochemical properties of MCCs with dissolution was established using an artificial neural network (ANN). The ANN model accurately predicted dissolution with low absolute and relative errors. The present study described a comprehensive QbD approach, statistical analysis, and ANN to comprehend and manage the effect of excipient variability on the design space. Full article
(This article belongs to the Special Issue Excipients Used in Pharmaceutical Dosage Forms)
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25 pages, 4310 KiB  
Article
New Insight into the Impact of Effervescence on Gel Layer Microstructure and Drug Release of Effervescent Matrices Using Combined Mechanical and Imaging Characterisation Techniques
by Pornsit Chaiya, Catleya Rojviriya, Wiwat Pichayakorn and Thawatchai Phaechamud
Pharmaceutics 2022, 14(11), 2299; https://doi.org/10.3390/pharmaceutics14112299 - 26 Oct 2022
Cited by 7 | Viewed by 2164
Abstract
Gel layer characteristics play a crucial role in hydrophilic hydroxypropyl methylcellulose (HPMC) matrix development. Effervescent agents have the potential to affect the gel layer microstructures. This study aimed to investigate the influence of effervescence on the microstructure of the gel layer around HPMC [...] Read more.
Gel layer characteristics play a crucial role in hydrophilic hydroxypropyl methylcellulose (HPMC) matrix development. Effervescent agents have the potential to affect the gel layer microstructures. This study aimed to investigate the influence of effervescence on the microstructure of the gel layer around HPMC matrices using a combination of texture analysis and imaging techniques. The relationship with drug release profile and release mechanisms were also examined. The high amounts of effervescent agents promoted a rapid carbonation reaction, resulting in a high gel layer formation with a low gel strength through texture analysis. This finding was ascribed to the enhanced surface roughness and porosity observed under digital microscopy and microporous structure of the gel layer under scanning electron microscopy. The reconstructed three-dimensional images from synchrotron radiation X-ray tomographic microscopy notably exhibited the interconnected pores of various sizes from the carbonation reaction of effervescent and microporous networks, indicating the gel layer on the tablet surface. Notably, effervescence promoted the increase in interconnected porosities, which directly influenced the strength of the gel layer microstructure, drug release patterns and release mechanism of the effervescent matrix tablet. Therefore, combined mechanical characterisation and imaging techniques can provide new insights into the role of effervescent agents on the gel layer microstructure, and describe the relationship of drug release patterns and release mechanism of matrix tablets. Full article
(This article belongs to the Special Issue Excipients Used in Pharmaceutical Dosage Forms)
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12 pages, 3237 KiB  
Article
Design, Preparation and Evaluation of Supramolecular Complexes with Curcumin for Enhanced Cytotoxicity in Breast Cancer Cell Lines
by Hamdy Abdelkader, Adel Al Fatease, Zeinab Fathalla, Mai E. Shoman, Heba A. Abou-Taleb and Mohammed A. S. Abourehab
Pharmaceutics 2022, 14(11), 2283; https://doi.org/10.3390/pharmaceutics14112283 - 25 Oct 2022
Cited by 4 | Viewed by 1270
Abstract
Curcumin is one of the most researched phytochemicals by pharmacologists and formulation scientists to unleash its potential therapeutic benefits and tackle inherent biopharmaceutic problems. In this study, the native β-cyclodextrin (CD) and three derivatives, namely, Captisol (sulfobutyl ether β-CD), hydroxypropyl β-cyclodextrin, and hydroxyethyl [...] Read more.
Curcumin is one of the most researched phytochemicals by pharmacologists and formulation scientists to unleash its potential therapeutic benefits and tackle inherent biopharmaceutic problems. In this study, the native β-cyclodextrin (CD) and three derivatives, namely, Captisol (sulfobutyl ether β-CD), hydroxypropyl β-cyclodextrin, and hydroxyethyl β-cyclodextrin were investigated for inclusion complexes with curcumin using two preparation methods (physical mixing and solvent evaporation). The prepared complexes were studied for docking, solubility, FTIR, DSC, XRD, and dissolution rates. The best-fitting curcumin: cyclodextrins (the latter of the two CDs) were evaluated for cytotoxicity using human breast cell lines (MCF-7). Dose-dependent cytotoxicity was recorded as IC50% for curcumin, curcumin: hydroxyethyl β-cyclodextrin, and curcumin: hydroxypropyl β-cyclodextrin were 7.33, 7.28, and 19.05 µg/mL, respectively. These research findings indicate a protective role for the curcumin: hydroxypropyl β-cyclodextrin complex on the direct cell lines of MCF-7. Full article
(This article belongs to the Special Issue Excipients Used in Pharmaceutical Dosage Forms)
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16 pages, 2799 KiB  
Article
Evaluation of Hydroxyethyl Cellulose Grades as the Main Matrix Former to Produce 3D-Printed Controlled-Release Dosage Forms
by David Hartzke, Axel Pössl, Peggy Schlupp and Frank E. Runkel
Pharmaceutics 2022, 14(10), 2103; https://doi.org/10.3390/pharmaceutics14102103 - 1 Oct 2022
Cited by 2 | Viewed by 1899
Abstract
Diclofenac sodium tablets were successfully prepared via hot-melt extrusion (HME) and fused deposition modeling (FDM), using different molecular-weight (Mw) grades of hydroxyethyl cellulose (HEC) as the main excipient. Hydroxypropyl cellulose (HPC) was added to facilitate HME and to produce drug-loaded, uniform filaments. The [...] Read more.
Diclofenac sodium tablets were successfully prepared via hot-melt extrusion (HME) and fused deposition modeling (FDM), using different molecular-weight (Mw) grades of hydroxyethyl cellulose (HEC) as the main excipient. Hydroxypropyl cellulose (HPC) was added to facilitate HME and to produce drug-loaded, uniform filaments. The effect of the HEC grades (90–1000 kDa) on the processability of HME and FDM was assessed. Mechanical properties of the filaments were evaluated using the three-point bend (3PB) test. Breaking stress and distance were set in relation to the filament feedability to identify printer-specific thresholds that enable proper feeding. The study demonstrated that despite the HEC grade used, all formulations were at least printable. However, only the HEC L formulation was feedable, showing the highest breaking stress (29.40 ± 1.52 MPa) and distance (1.54 ± 0.08 mm). Tablet drug release showed that the release was Mw dependent up to a certain HEC Mw limit (720 kDa). Overall, the release was driven by anomalous transport due to drug diffusion and polymer erosion. The results indicate that despite being underused in FDM, HEC is a suitable main excipient for 3D-printed dosage forms. More research on underutilized polymers in FDM should be encouraged to increase the limited availability. Full article
(This article belongs to the Special Issue Excipients Used in Pharmaceutical Dosage Forms)
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16 pages, 3607 KiB  
Article
Particle Agglomeration of Acid-Modified Tapioca Starches: Characterization and Use as Direct Compression Fillers in Tablets
by Chaipat Siriwachirachai and Thaned Pongjanyakul
Pharmaceutics 2022, 14(6), 1245; https://doi.org/10.3390/pharmaceutics14061245 - 12 Jun 2022
Cited by 5 | Viewed by 2256
Abstract
Acid-modified tapioca starches (AMTSs) possessed good compressibility but showed poor particle flowability for preparing tablets by the direct compression method. The aims of this work were to prepare and characterize AMTS agglomerates using polyvinylpyrrolidone (PVP) as an agglomerating agent. The dilution potential and [...] Read more.
Acid-modified tapioca starches (AMTSs) possessed good compressibility but showed poor particle flowability for preparing tablets by the direct compression method. The aims of this work were to prepare and characterize AMTS agglomerates using polyvinylpyrrolidone (PVP) as an agglomerating agent. The dilution potential and stability studies of the AMTS agglomerates were investigated. The results showed that particle enlargement of TS and AMTS could be achieved via agglomeration using PVP. The thermal behavior and molecular interaction of the agglomerates were revealed using DSC and FTIR spectroscopy, respectively. An increase in PVP concentrations resulted in greater particle strength of the TS agglomerates and a higher acid concentration for modification enhanced the strength of the AMTS agglomerates. All agglomerates presented good particle flowability. Moreover, the AMTS agglomerates provided higher compressibility hardness than the TS agglomerates. The addition of PVP could extend the disintegration time and slow drug dissolution from the agglomerate tablets. The humidity of the storage conditions influenced the thickness and hardness of the AMTS agglomerate tablets, and good physical and chemical stability of the tablets was obtained under ambient conditions and in the refrigerator. Furthermore, the AMTS agglomerates displayed good carrying capacity and possessed desirable characteristics for use in direct compression tablets. Full article
(This article belongs to the Special Issue Excipients Used in Pharmaceutical Dosage Forms)
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