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The AAPS Journal Jan 2022The work aimed to develop the Absorption Driven Drug Formulation (ADDF) concept, which is a new approach in formulation development to ensure that the drug product meets...
The work aimed to develop the Absorption Driven Drug Formulation (ADDF) concept, which is a new approach in formulation development to ensure that the drug product meets the expected absorption rate. The concept is built on the solubility-permeability interplay and the rate of supersaturation as the driving force of absorption. This paper presents the first case study using the ADDF concept where not only dissolution and solubility but also permeation of the drug is considered in every step of the formulation development. For that reason, parallel artificial membrane permeability assay (PAMPA) was used for excipient selection, small volume dissolution-permeation apparatus was used for testing amorphous solid dispersions (ASDs), and large volume dissolution-permeation tests were carried out to characterize the final dosage forms. The API-excipient interaction studies on PAMPA indicated differences when different fillers or surfactants were studied. These differences were then confirmed with small volume dissolution-permeation assays where the addition of Tween 80 to the ASDs decreased the flux dramatically. Also, the early indication of sorbitol's advantage over mannitol by PAMPA has been confirmed in the investigation of the final dosage forms by large-scale dissolution-permeation tests. This difference between the fillers was observed in vivo as well. The presented case study demonstrated that the ADDF concept opens a new perspective in generic formulation development using fast and cost-effective flux-based screening methods in order to meet the bioequivalence criteria. Graphical Abstract.
Topics: Drug Compounding; Drug Development; Drug Liberation; Drugs, Generic; Excipients; Humans; Membranes, Artificial; Permeability; Pharmaceutical Preparations; Proof of Concept Study; Solubility; Surface-Active Agents; Therapeutic Equivalency
PubMed: 34988721
DOI: 10.1208/s12248-021-00668-9 -
Chemical & Pharmaceutical Bulletin 2022Albumin, the most abundant protein in human serum, is applied to various diseases as a drug delivery carrier because of its superior blood retention, high... (Review)
Review
Albumin, the most abundant protein in human serum, is applied to various diseases as a drug delivery carrier because of its superior blood retention, high biocompatibility, and a wide variety of drug binding abilities. Albumin is known to distribute widely in the blood and various interstitial fluids and organs. Different albumin receptors skillfully regulate the distribution characteristics of albumin in the body. Albumin receptors are a group of diverse proteins, such as FcRn, gp60, gp18, megalin, cubilin, SPARC, and CD36. Their tissue distributions in vivo are unique, with different albumin's recognition sites. Therefore, the distribution of albumin in vivo is ingeniously controlled by these multiple albumin receptors. Reevaluation of these albumin receptors opens up new possibilities for applying albumin as a drug delivery carrier. If the tissue distributions of albumin receptors were known and the albumin recognition site of the receptor was identified, organ-specific active targeting would be possible. In this review, we would like to scrutinize what is currently known and share information to develop next-generation albumin carriers that focus on interactions with albumin receptors.
Topics: Albumins; Drug Delivery Systems; Excipients; Humans; Receptors, Albumin; Tissue Distribution
PubMed: 35491188
DOI: 10.1248/cpb.c21-01024 -
Drug Delivery Dec 2020Amorphous solid dispersions (ASDs) can increase the oral bioavailability of poorly soluble drugs. However, their use in drug development is comparably rare due to a lack... (Review)
Review
Amorphous solid dispersions (ASDs) can increase the oral bioavailability of poorly soluble drugs. However, their use in drug development is comparably rare due to a lack of basic understanding of mechanisms governing drug liberation and absorption . Furthermore, the lack of a unified nomenclature hampers the interpretation and classification of research data. In this review, we therefore summarize and conceptualize mechanisms covering the dissolution of ASDs, formation of supersaturated ASD solutions, factors responsible for solution stabilization, drug uptake from ASD solutions, and drug distribution within these complex systems as well as effects of excipients. Furthermore, we discuss the importance of these findings on the development of ASDs. This improved overall understanding of these mechanisms will facilitate a rational ASD formulation development and will serve as a basis for further mechanistic research on drug delivery by ASDs.
Topics: Biological Availability; Crystallization; Delayed-Action Preparations; Drug Liberation; Drug Stability; Excipients; Pharmacokinetics; Solubility; Surface-Active Agents; Technology, Pharmaceutical
PubMed: 31885288
DOI: 10.1080/10717544.2019.1704940 -
PloS One 2022This work proposes a methodology for the design, development, optimisation, and evaluation of amorphous rosuvastatin calcium tablets (BCS class II drug). The main goal...
This work proposes a methodology for the design, development, optimisation, and evaluation of amorphous rosuvastatin calcium tablets (BCS class II drug). The main goal was to ensure rapid disintegration and high dissolution rate of the active ingredient, thus enhancing its bioavailability. The design started from a careful selection of excipients, which due to their characteristics and proportions within the formulation allowed the use of their properties such as fluidity or granulometric distribution. The formulation was characterised using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD) methods. The galenic SeDeM methodology was used to establish the profile of the active ingredient-excipient mixture and guarantee its suitability for producing tablets by the direct compression method. The results demonstrate that the amorphous rosuvastatin calcium tablets formulation developed made it possible to obtain cost-effective tablets by direct compression with optimal pharmacotechnical characteristics that showed a remarkable disintegration and dissolution rate. The manufactured tablets complied with the pharmacopoeia guidelines regarding content uniformity, tablet hardness, thickness, friability, in vitro disintegration time and dissolution profile.
Topics: Calcium; Calorimetry, Differential Scanning; Excipients; Rosuvastatin Calcium; Solubility; Spectroscopy, Fourier Transform Infrared; Tablets; X-Ray Diffraction
PubMed: 35312730
DOI: 10.1371/journal.pone.0265263 -
Molecules (Basel, Switzerland) Feb 2023Two-dimensional materials have wide ranging applications in electronic devices and catalysts owing to their unique properties. Boron-based compounds, which exhibit a...
Two-dimensional materials have wide ranging applications in electronic devices and catalysts owing to their unique properties. Boron-based compounds, which exhibit a polymorphic nature, are an attractive choice for developing boron-based two-dimensional materials. Among them, rhombohedral boron monosulfide (r-BS) has recently attracted considerable attention owing to its unique layered structure similar to that of transition metal dichalcogenides and a layer-dependent bandgap. However, experimental evidence that clarifies the charge carrier type in the r-BS semiconductor is lacking. In this study, we synthesized r-BS and evaluated its performance as a semiconductor by measuring the Seebeck coefficient and photo-electrochemical responses. The properties unique to p-type semiconductors were observed in both measurements, indicating that the synthesized r-BS is a p-type semiconductor. Moreover, a distinct Fano resonance was observed in Fourier transform infrared absorption spectroscopy, which was ascribed to the Fano resonance between the E(2) (TO) phonon mode and electrons in the band structures of r-BS, indicating that the p-type carrier was intrinsically doped in the synthesized r-BS. These results demonstrate the potential future application prospects of r-BS.
Topics: Boron; Electronics; Electrons; Excipients; Semiconductors
PubMed: 36838883
DOI: 10.3390/molecules28041896 -
BioMed Research International 2022Pharmaceutical excipients are compounds or substances other than API which are added to a dosage form, these excipients basically act as carriers, binders, bulk forming...
Pharmaceutical excipients are compounds or substances other than API which are added to a dosage form, these excipients basically act as carriers, binders, bulk forming agents, colorants, and flavouring agents, and few excipients are even used to enhance the activity of active pharmaceutical ingredient (API) and various more properties. However, despite of these properties, there are problems with the synthetic excipients such as the possibility of causing toxicity, inflammation, autoimmune responses, lack of intrinsic bioactivity and biocompatibility, expensive procedures for synthesis, and water solubility. However, starch as an excipient can overcome all these problems in one go. It is inexpensive, there is no toxicity or immune response, and it is biocompatible in nature. It is very less used as an excipient because of its high digestibility and swelling index, high glycemic index, paste clarity, film-forming property, crystalline properties, etc. All these properties of starch can be altered by a few modification processes such as physical modification, genetic modification, and chemical modification, which can be used to reduce its digestibility and glycemic index of starch, improve its film-forming properties, and increase its paste clarity. Changes in some of the molecular bonds which improve its properties such as binding, crystalline structure, and retrogradation make starch perfect to be used as a pharmaceutical excipient. This research work provides the structural modifications of native starch which can be applicable in advanced drug delivery. The major contributions of the paper are advances in the modification of native starch molecules such as physically, chemically, enzymatically, and genetically traditional crop modification to yield a novel molecule with significant potential for use in the pharmaceutical industry for targeted drug delivery systems.
Topics: Drug Delivery Systems; Excipients; Solubility; Starch
PubMed: 35993055
DOI: 10.1155/2022/2188940 -
TheScientificWorldJournal 2023Natural polymers such as pectin have gained increased utilization in pharmaceutical and biotechnology sectors because they are affordable, easily accessible, nontoxic,...
Natural polymers such as pectin have gained increased utilization in pharmaceutical and biotechnology sectors because they are affordable, easily accessible, nontoxic, and chemically modifiable, with the potential to be biodegradable and biocompatible. (plantain) peels make up 30-40% of the overall weight of the fruit. The extraction of pectin from these residues can therefore be viewed as a possible waste of wealth. This study, therefore, focused on evaluating the suspending properties of pectin obtained from (plantain) peels (through acid and alkaline extraction) and presented an alternative suspending agent in the pharmaceutical formulation of suspensions. The unripe peels of were acquired and authenticated at the Department of Pharmacognosy, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana. Pectin was extracted from the peels using both acid and alkaline extraction processes, respectively, characterized, and evaluated for its phytochemical properties. Different concentrations of the acid and alkaline pectin extracts were employed as a suspending agent in paracetamol suspensions, using acacia gum as a standard. The pectin yields obtained were 4.88% and 7.61% for the acid and alkaline extraction processes, respectively, while phytochemical screening revealed the presence of glycosides, tannins, saponins, and phenols in both extracts. The alkaline pectin extract recorded higher equivalent weight, degree of esterification, ash content, and crude content than the acid pectin extract, while FTIR identified similar functional groups in both acid and alkaline pectin extracts. The test suspensions reported significant differences ( < 0.05) in flow rates, ease of redispersion, sedimentation volumes, and rates compared with acacia gum. Moreover, when the acid and alkaline pectin extracts were compared, significant differences ( < 0.05) were observed in sedimentation rates and sedimentation volumes, suggesting that the extraction method may affect suspending properties. Ultimately, the alkaline pectin extract had better suspending properties than the acid pectin extract; however, they both can be used as an alternative to acacia gum as a suspending agent.
Topics: Pectins; Excipients; Musa; Plantago; Drug Compounding; Gum Arabic; Pharmacy; Phytochemicals
PubMed: 37808477
DOI: 10.1155/2023/8898045 -
Molecules (Basel, Switzerland) Nov 2022The chemical stability of diphenhydramine (DIPH), azelastine (AZE) and bepotastine (BEPO) was examined in solutions and solids. The drugs were subjected to high...
Chemical Stability Study of H Antihistaminic Drugs from the First and the Second Generations, Diphenhydramine, Azelastine and Bepotastine, in Pure APIs and in the Presence of Two Excipients, Citric Acid and Polyvinyl Alcohol.
The chemical stability of diphenhydramine (DIPH), azelastine (AZE) and bepotastine (BEPO) was examined in solutions and solids. The drugs were subjected to high temperature (70 °C for 35 h) or UV/VIS light (18.902−94.510 kJ/m2) at pH 1−13, to examine their percentage degradation and kinetics of degradation. Further, the stability of solid DIPH, AZE and BEPO was examined in the presence of excipients of different reactivity, i.e., citric acid (CA) and polyvinyl alcohol (PVA) under high temperature/high humidity (70 °C/80% RH) or UV/VIS light (94.510 kJ/m2). Under high temperature, DIPH degraded visibly (>19%) at pH 1 and 4, AZE was shown stable, while the degradation of BEPO was rather high (>17%) in all pH conditions. Under UV/VIS irradiation all the drugs were shown labile with degradation in the range 5.5−96.3%. As far as the solid mixtures were concerned, all drugs interacted with excipients, especially under high temperature/high humidity or UV/VIS light. As a result, DIPH, AZE and BEPO were compared in terms of their stability, with regard to their different structures and acid/base properties. All these results may be helpful for manufacturing, storing and applying these drugs in their topical (skin, nasal and ocular), oral and injectable formulations.
Topics: Excipients; Drug Stability; Polyvinyl Alcohol; Diphenhydramine; Citric Acid; Histamine Antagonists
PubMed: 36500415
DOI: 10.3390/molecules27238322 -
Scientific Reports Oct 2022Improving boiling is challenging due to the unpredictable nature of bubbles. One way to enhance boiling is with surfactants, which alter the solid-liquid and...
Improving boiling is challenging due to the unpredictable nature of bubbles. One way to enhance boiling is with surfactants, which alter the solid-liquid and liquid-vapor interfaces. The conventional wisdom established by previous studies suggests that heat transfer enhancement is optimized near the critical micelle concentration (CMC), which is an equilibrium property that depends on surfactant type. However, these studies only tested a limited number of surfactants over small concentration ranges. Here, we test a larger variety of nonionic and anionic surfactants over the widest concentration range and find that a universal, optimal concentration range exists, irrespective of CMC. To explain this, we show that surfactant-enhanced boiling is controlled by two competing phenomena: (1) the dynamic adsorption of surfactants to the interfaces and (2) the increase in liquid dynamic viscosity at very high surfactant concentrations. This dynamic adsorption is time-limited by the millisecond-lifetime of bubbles on the boiling surface-much shorter than the timescales required to see equilibrium behaviors such as CMC. At very high concentrations, increased viscosity inhibits rapid bubble growth, reducing heat transfer. We combine the effects of adsorption and viscosity through a simple proportionality, providing a succinct and useful understanding of this enhancement behavior for boiling applications.
Topics: Surface-Active Agents; Adsorption; Micelles; Pulmonary Surfactants; Excipients
PubMed: 36307430
DOI: 10.1038/s41598-022-21313-1 -
PloS One 2021Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics...
Human serum albumin (HSA) has been widely used as a pharmaceutical excipient in Botulinum toxin serotype A (BoNT/A) products that are indicated for use in therapeutics and cosmetics. However, HSA as a human-derived material has some concerns, such as the potential risk of transmission of infectious agents, an insufficient supply, and difficulty in maintaining a certain quality. For those reasons, newly developed BoNT/A products (CORETOX®, Medytox, Inc., Republic of Korea) contained polysorbate 20, a non-human-derived excipient, to replace the HSA. However, most safety studies of polysorbate 20 have been conducted with non-invasive routes of administration, and thus there are a few studies on the safety of polysorbate 20 when administered intramuscularly. To secure the in vivo safety profile of polysorbate 20, a four-week repeated intramuscular dose toxicity study (0.02, 0.1, and 0.4 mg/kg, one injection every two weeks for a total of three injections) was conducted in 66 Sprague-Dawley (SD) rats. An intradermal irritation study was further conducted with 18 New Zealand White (NZW) rabbits. The toxicological evaluation of HSA (0.06 and 0.12 mg/kg) was also carried out as a comparative substance. Systemic and local toxicities were not observed in any of the SD rats or NZW rabbits based on clinical signs, body weight, hematology, clinical biochemistry, macroscopic findings on necropsy, histopathology of the injection site, and allergic reactions. The current study suggested that intramuscular administration of polysorbate 20 was considered to be safe at a level similar to that of HSA, which has an in vivo safety profile accumulated over the years. This provided the basis for the in vivo safety profile of polysorbate 20 administered intramuscularly and the scientific reliability of the use of polysorbate 20 as an alternative to HSA, which is used as an excipient for various pharmaceuticals in terms of its safety.
Topics: Animals; Botulinum Toxins; Botulism; Excipients; Humans; Polysorbates; Rabbits; Rats; Rats, Sprague-Dawley; Republic of Korea; Serum Albumin, Human
PubMed: 34449810
DOI: 10.1371/journal.pone.0256869