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Polimery W Medycynie 2022Irvingia gabonensis kernel polymer has gained attention in drug delivery systems because of its compatibility and degradation under natural and physiological conditions.
BACKGROUND
Irvingia gabonensis kernel polymer has gained attention in drug delivery systems because of its compatibility and degradation under natural and physiological conditions.
OBJECTIVES
This study aimed to evaluate Irvingia gabonensis polymer as a matrix system for the controlled delivery of ibuprofen in comparison to xanthan gum and hydroxypropylmethylcellulose (HPMC).
MATERIAL AND METHODS
Irvingia gabonensis polymer was extracted using established methods and dried using the ovenand freeze-drying methods. Ibuprofen tablets were prepared by direct compression and the effects of polymer concentration (10-50%), excipients (lactose, microcrystalline cellulose and dicalcium phosphate dihydrate) and polymers (xanthan gum and HPMC) on the mechanical and drug release properties of the tablets were evaluated. Density measurements and the Heckel and Kawakita equations were used to determine the compression properties of the tablets. Friability, crushing strength and the crushing strength-friability ratio (CSFR) were used to evaluate the mechanical properties of the tablets, while dissolution times were used to evaluate drug release from the matrices. The drug release mechanisms were determined by fitting the dissolution data into classic kinetic equations.
RESULTS
Irvingia gabonensis polymer deformed plastically with a fast onset and a high amount of plastic deformation compared with xanthan gum and HPMC. This polymer was directly compressible and formed intact non-disintegrating tablets; the mechanical and dissolution properties of Irvingia gabonensis polymer tablets generally decreased with increasing concentration of ibuprofen. The ranking of dissolution times was xanthan gum > freeze-dried Irvingia gabonensis > HPMC > oven-dried Irvingia gabonensis. The addition of the excipients improved the mechanical properties of the tablets, aided ibuprofen release, and altered the release kinetics, which was largely defined by the Korsmeyer-Peppas model. Increasing the proportion of xanthan gum and HPMC in the matrices resulted in a decreased amount of ibuprofen released after 9 h, with xanthan gum having a greater effect.
CONCLUSIONS
Irvingia gabonensis polymer matrices may be effective in the preparation of controlled release tablets, and their right combination with xanthan gum or HPMC could provide a time-independent release for longer durations.
Topics: Ibuprofen; Polymers; Excipients; Drug Delivery Systems; Hypromellose Derivatives; Tablets; Delayed-Action Preparations; Solubility
PubMed: 36268745
DOI: 10.17219/pim/153521 -
Opportunities for milk and milk-related systems as 'new' low-cost excipient drug delivery materials.Advanced Drug Delivery Reviews Apr 2022Milk is well recognised as an amazing delivery system for essential lipids, poorly soluble nutrients, sugars, amino acids and delivery of critical biological molecules... (Review)
Review
Milk is well recognised as an amazing delivery system for essential lipids, poorly soluble nutrients, sugars, amino acids and delivery of critical biological molecules to sustain the infant and adult alike. It is also a safe and abundant resource with potential to act as a low-cost material for formulation of medicines, especially for paediatric patients and those in low economy settings. However, its use in low cost formulations has never developed beyond preclinical evaluation. Reasons for this are several-fold including variable composition and therefore regulatory challenges, as well as a lack of clear understanding around when milk or milk-related materials like infant formula could best be deployed by linking drug properties with excipient composition attributes, especially when taking digestion into account. This review collects the current understanding around these issues. It is apparent from the evolving understanding that while milk may be a bridge too far for translation as an excipient, infant formula is positioned to play a key role in the future because, as a powder-based excipient, it has the performance benefits of milk powder together with the controlled specifications during manufacture and versatility of application to function as a low cost lipid excipient to enable potential translation for the oral delivery of poorly water soluble drugs for key populations including paediatrics and low economy medicines.
Topics: Adult; Animals; Child; Drug Delivery Systems; Excipients; Humans; Milk; Pharmaceutical Preparations; Powders; Solubility
PubMed: 35143892
DOI: 10.1016/j.addr.2022.114139 -
International Journal of Pharmaceutics Dec 2022The mechanism of action of excipients eliciting sex differences in drug bioavailability is poorly understood. In this study, the excipients Cremophor RH 40 (PEG 40...
The mechanism of action of excipients eliciting sex differences in drug bioavailability is poorly understood. In this study, the excipients Cremophor RH 40 (PEG 40 hydrogenated castor oil), Poloxamer 188 (2-methyloxirane) and Tween 80 (polyoxyethylene (80) sorbitan monooleate) were screened at 0.07 - 5% concentrations for their effect on ranitidine bioavailability in male and female Wistar rats. We show that all excipient concentrations significantly increased ranitidine bioavailability in male, but not female, rats. The effect of these excipients on the intestinal efflux transporters P-glycoprotein (P-gp), breast cancer resistant protein (BCRP) and multi-drug resistant protein 2 (MRP2) were also monitored. Measured by ELISA assay, in male rats, peak reductions in intestinal P-gp protein expression occurred in the presence of 1% Cremophor RH 40 and Poloxamer 188 and 0.5% Tween 80. In contrast, no distinct changes were observed in female intestinal P-gp expression. Unlike P-gp, all excipients had a positive effect on MRP2 protein expression - albeit only in males - in a concentration-dependent manner. The excipients did not modulate intestinal BCRP protein expression in either sex. Endogenous hormones and a nuclear receptor (testosterone, oestradiol and pregnane X receptor; PXR) that are purported to regulate intestinal efflux membrane transporter expression were also quantified. In the presence of all excipients, testosterone levels significantly elevated in males, although PXR levels reduced at similar rates in both sexes. No significant effects were identified in oestradiol levels in male and female rats. It is clear that excipients are not inert and their pathway for modulating drug response is multi-dimensional and specific between sexes. This study showed that excipients increased drug bioavailability of a P-gp drug substrate due to its reductive effect on intestinal P-gp expression; we propose that this link may be due to the excipients modulating fundamental testosterone levels. Understanding the implication of excipients on intestinal physiology and hormone levels can therefore improve pharmaceutical design, clinical efficacy and instigate next generation personalised, sex-specific formulations.
Topics: Male; Female; Rats; Animals; Excipients; Biological Availability; Polysorbates; ATP Binding Cassette Transporter, Subfamily G, Member 2; Ranitidine; Poloxamer; Rats, Wistar; Neoplasm Proteins; Estradiol; Testosterone
PubMed: 36336203
DOI: 10.1016/j.ijpharm.2022.122365 -
Pharmaceutical Research Dec 2021
Topics: Chemistry, Pharmaceutical; Excipients
PubMed: 34931284
DOI: 10.1007/s11095-021-03157-y -
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 -
AAPS PharmSciTech Dec 2011Reactive impurities in pharmaceutical excipients could cause drug product instability, leading to decreased product performance, loss in potency, and/or formation of... (Review)
Review
Reactive impurities in pharmaceutical excipients could cause drug product instability, leading to decreased product performance, loss in potency, and/or formation of potentially toxic degradants. The levels of reactive impurities in excipients may vary between lots and vendors. Screening of excipients for these impurities and a thorough understanding of their potential interaction with drug candidates during early formulation development ensure robust drug product development. In this review paper, excipient impurities are categorized into six major classes, including reducing sugars, aldehydes, peroxides, metals, nitrate/nitrite, and organic acids. The sources of generation, the analytical method for detection, the stability of impurities upon storage and processing, and the potential reactions with drug candidates of these impurities are reviewed. Specific examples of drug-excipient impurity interaction from internal research and literature are provided. Mitigation strategies and corrective measures are also discussed.
Topics: Chemistry, Pharmaceutical; Drug Compounding; Drug Contamination; Drug Stability; Drug-Related Side Effects and Adverse Reactions; Excipients; Models, Chemical; Pharmaceutical Preparations; Technology, Pharmaceutical
PubMed: 21948318
DOI: 10.1208/s12249-011-9677-z -
Acta Pharmaceutica (Zagreb, Croatia) Sep 2016Nanoindentation allows quantitative determination of a material's response to stress such as elastic and plastic deformation or fracture tendency. Key instruments that... (Review)
Review
Nanoindentation allows quantitative determination of a material's response to stress such as elastic and plastic deformation or fracture tendency. Key instruments that have enabled great advances in nanomechanical studies are the instrumented nanoindenter and atomic force microscopy. The versatility of these instruments lies in their capability to measure local mechanical response, in very small volumes and depths, while monitoring time, displacement and force with high accuracy and precision. This review highlights the application of nanoindentation for mechanical characterization of pharmaceutical materials in the preformulation phase (primary investigation of crystalline active ingredients and excipients). With nanoindentation, mechanical response can be assessed with respect to crystal structure. The technique is valuable for mechanical screening of a material at an early development phase in order to predict and better control the processes in which a material is exposed to stress such as milling and compression.
Topics: Chemistry, Pharmaceutical; Drug Compounding; Elastic Modulus; Excipients; Hardness; Mechanical Phenomena; Microscopy, Atomic Force; Nanotechnology; Organic Chemicals; Pharmaceutical Preparations; Surface Properties
PubMed: 27383883
DOI: 10.1515/acph-2016-0032 -
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 -
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