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Pharmaceutics May 2021This article highlights the advantages of pharmaceutical continuous melt granulation by twin-screw extrusion. The different melt granulation process options and... (Review)
Review
This article highlights the advantages of pharmaceutical continuous melt granulation by twin-screw extrusion. The different melt granulation process options and excipients are described and compared, and a case is made for expanded use of twin-screw melt granulation since it is a flexible and continuous process. Methods for binder selection are profiled with a focus on rheology and physical stability impacts. For twin-screw melt granulation, the mechanism of granulation and process impact on granule properties are described. Pharmaceutical applications of melt granulation ranging from immediate release of soluble and insoluble APIs, taste-masking, and sustained release formulation are reviewed, demonstrating the range of possibilities afforded by twin-screw melt granulation.
PubMed: 34066332
DOI: 10.3390/pharmaceutics13050665 -
Polymers Jun 2022Glucomannan (GM)-a polysaccharide generally extracted from the tuber of -has great potential as a filler-binder in direct compression, disintegrant in tablets, or... (Review)
Review
Glucomannan (GM)-a polysaccharide generally extracted from the tuber of -has great potential as a filler-binder in direct compression, disintegrant in tablets, or gelling agent due to its strong hydrophilicity and extremely high viscosity. However, it has poor water resistance and low mechanical strength when used as an excipient in solid form. Several physical and chemical modifications have been carried out to improve these drawbacks. Chemical modification affects the characteristics of GM based on the DS. Carboxymethylation improves GM functionality by modifying its solubility and viscosity, which in turn allows it to bind water more efficiently and thus improve its elongation and gel homogeneity. Meanwhile, physical modification enhances functionality through combination with other excipients to improve mechanical properties and modify swelling ability and drug release from the matrix. This review discusses extraction of GM and its modification to enhance its applicability as an excipient in solid form. Modified GM is a novel excipient applicable in the pharmaceutical industry for direct compression, as a tablet disintegrant, a film-forming agent, and for encapsulation of macromolecular compounds or drug carriers for controlled release.
PubMed: 35808596
DOI: 10.3390/polym14132550 -
Biotechnology and Bioengineering Jun 2019Nowadays, chemically defined cell culture media (CCM) have replaced serum- and hydrolysate-based media that rely on complex ingredients, such as yeast extracts or... (Review)
Review
Nowadays, chemically defined cell culture media (CCM) have replaced serum- and hydrolysate-based media that rely on complex ingredients, such as yeast extracts or peptones. Benefits include a significantly lower lot-to-lot variability, more efficient manufacturing by reduction to essential components, and the ability to exclude components that may negatively influence growth, viability, or productivity. Even though current chemically defined CCMs provide an excellent basis for various mammalian biotechnological processes, vitamin instabilities are known to be a key factor contributing to the variabilities still present in liquid CCM as well as to short storage times. In this review, the chemical degradation pathways and products for the most relevant vitamins for CCM will be discussed, with a focus on the effects of light, oxygen, heat, and other CCM compounds. Different approaches to stabilize vitamins in solution, such as replacement with analogs, encapsulation, or the addition of stabilizing compounds will also be reviewed. While these vitamins and vitamin stabilization approaches are presented here as particular for CCM, the application of these concepts can also be considered relevant for pharmaceutical, medical, and food supplement purposes. More precise knowledge regarding vitamin instabilities will contribute to stabilize future formulations and thus decrease residual lot-to-lot variability.
Topics: Animals; Biotechnology; Cell Culture Techniques; Culture Media; Drug Stability; Excipients; Hot Temperature; Humans; Light; Oxygen; Vitamins
PubMed: 30793282
DOI: 10.1002/bit.26942 -
Journal of Pharmacopuncture Dec 2022Polymers are the major constructive material of pharmaceutical formulations that play a prime role in designing effective drug-delivery systems and releasing drugs at... (Review)
Review
Polymers are the major constructive material of pharmaceutical formulations that play a prime role in designing effective drug-delivery systems and releasing drugs at their sites of application. Polymers are composed of multiple repeating units of high molecular mass components with attendant properties. Most synthetic polymers are non-biocompatible, expensive, and extremely inclined to deliver adverse impacts. Meanwhile, edible polymers obtained from natural sources have gained remarkable recognition for their promising use in modern medicine. Moreover, polymers derived from natural sources are generally preferred due to certain of their unique features such as abundant availability, biocompatibility, nontoxicity, economical, safe, and effective functions that fit the purpose. Polysaccharides including starch, cellulose, hemicellulose, pectin, and mucilage are identified as a major class of naturally obtained molecules that have a substantial role as functional polymers. This review summarizes the potential role of polysaccharides derived from vegetable sources such as adhesives, anticaking agents, binders, disintegrants, emulsifiers, film-framing agents, and thickeners. This is simply an opportunity to abandon synthetic excipients that hurt our bodies and think back to nature from where we originate.
PubMed: 36628349
DOI: 10.3831/KPI.2022.25.4.317 -
Pharmaceutics Dec 2021Co-processing is commonly used approach to improve functional characteristics of pharmaceutical excipients to become suitable for tablet production by direct...
Co-processing is commonly used approach to improve functional characteristics of pharmaceutical excipients to become suitable for tablet production by direct compression. This study aimed to improve tableting characteristics of lactose monohydrate (LMH) by co-processing by fluid-bed melt granulation with addition of hydrophilic (PEG 4000 and poloxamer 188) and lipophilic (glyceryl palmitostearate) meltable binders. In addition to binding purpose, hydrophilic and lipophilic excipients were added to achieve self-lubricating properties of mixture. Co-processed mixtures exhibit superior flow properties compared to pure LMH and comparable or better flowability relative to commercial excipient Ludipress. Compaction of mixtures co-processed with 20% PEG 4000 and 20% poloxamer 188 resulted in tablets with acceptable tensile strength (>2 MPa) and good lubricating properties (ejection and detachment stress values below 5 MPa) in a wide range of compression pressures. While the best lubricating properties were observed when glyceryl palmitostearate was used as meltable binder, obtained tablets failed to fulfil required mechanical characteristics. Although addition of meltable binder improves interparticle bonding, disintegration time was not prolonged compared to commercial excipient Ludipress. Co-processed mixtures containing 20% of either PEG 4000 or poloxamer 188 showed superior tabletability and lubricant properties relative to LMH and Ludipress and can be good candidates for tablet production by direct compression.
PubMed: 34959447
DOI: 10.3390/pharmaceutics13122165 -
The American Journal of Emergency... Nov 2022Dextromethorphan polistirex is an extended-release formulation of dextromethorphan hydrobromide, marketed as Delsym® (Reckitt; Parsippany, NJ), with a duration of...
Dextromethorphan polistirex is an extended-release formulation of dextromethorphan hydrobromide, marketed as Delsym® (Reckitt; Parsippany, NJ), with a duration of action roughly two to three times that of the standard formulation. The polistirex binder is responsible for the prolonged duration of action by slowing the release of active ingredient; the liberated dextromethorphan has unchanged pharmacokinetics and clinical effects. A 23-month-old male presented following a 900 mg (71.4 mg/kg) dextromethorphan polistirex ingestion 90 min prior. On arrival, he was unresponsive, tachycardic, and hypertensive with mydriasis, roving eye movements, rotary nystagmus, and opisthotonos. Approximately 90 min after arrival, he required intubation for airway protection. The blood dextromethorphan concentration from 75 min after arrival was 110 ng/mL (10-40 ng/ml therapeutic). He was extubated approximately 13 h after arrival and discharged that day. Most pediatric dextromethorphan overdoses produce mild symptoms that are not considered to be life-threatening. Life threatening overdoses are rare. The toxic dextromethorphan dose and blood concentration as well as the toxicokinetics of the polistirex formulation are not well defined. Our case suggests that a blood dextromethorphan concentration exceeding 100 ng/mL can be toxic in this age group, however further study is needed.
Topics: Humans; Child; Male; Infant; Child, Preschool; Dextromethorphan; Drug Overdose; Excipients; Delayed-Action Preparations; Nystagmus, Pathologic
PubMed: 35989201
DOI: 10.1016/j.ajem.2022.08.006 -
Pharmaceutics Feb 2021The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to...
The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable efficient formulation development. Therefore, the current study identified binder attributes affecting the binder effectiveness in a wet granulation process of a highly soluble model excipient (mannitol). For this formulation, higher binder effectiveness was linked to fast activation of the binder properties (i.e., fast binder dissolution kinetics combined with low viscosity attributes and good wetting properties by the binder). As the impact of binder attributes on the granulation process of a poorly soluble formulation (dicalcium phosphate) was previously investigated, this enabled a comprehensive comparison between both formulations in current research focusing on binder selection. This comparison revealed that binder attributes that are important to guide binder selection differ in function of the solubility of the formulation. The identification of critical binder attributes in the current study enables rational and efficient binder selection for twin-screw granulation of well soluble and poorly soluble formulations. Binder addition proved especially valuable for a poorly soluble formulation.
PubMed: 33546383
DOI: 10.3390/pharmaceutics13020210 -
TheScientificWorldJournal 2022Excipients are components other than active ingredients that are added to pharmaceutical formulations. Naturally sourced excipients are gradually gaining preeminence...
Excipients are components other than active ingredients that are added to pharmaceutical formulations. Naturally sourced excipients are gradually gaining preeminence over synthetically sourced excipients due to local availability and continuous supply. This study aimed to investigate the binding and disintegrating characteristics of gum extracted from the bark of tree. The bark of was harvested from Kwahu Asasraka in Ghana. The gum was extracted with ethanol (96%), and the percentage yield, phytochemical constituents, and flow characteristics were assessed. As a disintegrant, the gum was utilized to formulate granules at varying concentrations of 5% w/w and 10% w/w using starch as the standard. The gum was also utilized to prepare granules at varying concentrations of 10% w/v and 20% w/v as a binder, with tragacanth gum serving as the reference. Eight batches of tablets were produced from the granules. The formulated tablets from each batch were then subjected to quality control testing, which included uniformity of weight, friability, disintegration, hardness, drug content, and dissolution tests, respectively. Tannins, saponins, alkaloids, and glycosides were identified in the gum. The gum had a percentage yield of 67.75% and also exhibited good flow properties. All tablets passed the uniformity of weight, friability, disintegration, hardness, dissolution, and drug content tests, respectively. According to the findings of the study, gum can be utilized as an excipient in place of tragacanth and starch as a binder and disintegrant, respectively, in immediate-release tablets.
Topics: Chemistry, Pharmaceutical; Excipients; Melia azedarach; Solubility; Starch; Tablets; Tragacanth
PubMed: 35401058
DOI: 10.1155/2022/9810099 -
Molecules (Basel, Switzerland) May 2023Recently calcium alginate has been successfully applied to encapsulate asphalt rejuvenator, which can protect asphalt rejuvenator from early leakage and release asphalt...
Recently calcium alginate has been successfully applied to encapsulate asphalt rejuvenator, which can protect asphalt rejuvenator from early leakage and release asphalt rejuvenator when triggered by specific factors such as cracks. The interfacial adhesion property of asphalt binder with calcium alginate carrier is of great importance to its actual performance. In this paper, the molecular model of the interface region between asphalt binder and calcium alginate was established, and molecular dynamics simulations were performed on it to investigate the molecular interaction at the interface region. By extracting and processing the data during the simulation process, the interfacial adhesion behavior was expounded using the spreading coefficient (S), permeation depth and permeation degree. Furthermore, the interfacial adhesion strength was evaluated by adopting the interfacial adhesion work. Results showed that the value of S was greater than 0, implying that asphalt binder could wet the surface of calcium alginate. Saturate had the highest value of permeation degree, followed by resin, aromatic and asphaltene. However, asphalt binder could not infiltrate into the interior of TiO, only accumulating and spreading on the surface of TiO. The interfacial adhesion work of unaged and aged asphalt binder to calcium alginate was -114.18 mJ/m and -186.37 mJ/m, respectively, similar to that of asphalt-aggregate interface. The van der Waals interactions contributed the most to the formation of the interfacial adhesion strength. In addition, a certain degree aging of asphalt binder and addition of titanium dioxide in the calcium alginate carrier were helpful to enhance the interfacial adhesion strength.
Topics: Humans; Aged; Physical Phenomena; Tissue Adhesions; Excipients; Alginates; Molecular Dynamics Simulation
PubMed: 37298923
DOI: 10.3390/molecules28114447 -
Materials (Basel, Switzerland) Oct 2019Polymers constitute the most important group of excipients utilized in modern pharmaceutical technology, playing an essential role in the development of drug dosage... (Review)
Review
Polymers constitute the most important group of excipients utilized in modern pharmaceutical technology, playing an essential role in the development of drug dosage forms. Synthetic, semisynthetic, and natural polymeric materials offer opportunities to overcome different formulative challenges and to design novel dosage forms for controlled release or for site-specific drug delivery. They are extensively used to design therapeutic systems, modify drug release, or mask unpleasant drug taste. Cellulose derivatives are characterized by different physicochemical properties, such as swellability, viscosity, biodegradability, pH dependency, or mucoadhesion, which determine their use in industry. One cellulose derivative with widespread application is ethylcellulose. Ethylcellulose is used in pharmaceutical technology as a coating agent, flavoring fixative, binder, filler, film-former, drug carrier, or stabilizer. The aim of this article is to provide a broad overview of ethylcellulose utilization for pharmaceutical purposes, with particular emphasis on its multidirectional role in the development of oral and topical drug dosage forms.
PubMed: 31627271
DOI: 10.3390/ma12203386