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The use of chemical permeation enhancers (PEs) is the most widely tested approach to improve oral absorption of low permeability active agents, as represented by peptides. Several hundred PEs increase intestinal permeability in preclinical bioassays, yet few have progressed to clinical testing and, of those, only incremental increases in oral bioavailability (BA) have been observed. Still, average BA values of ~1% were sufficient for two recent FDA approvals of semaglutide and octreotide oral formulations. PEs are typically screened in static in vitro and ex-vivo models where co-presentation of active agent and PE in high concentrations allows the PE to alter barrier integrity with sufficient contact time to promote flux across the intestinal epithelium. The capacity to maintain high concentrations of co-presented agents at the epithelium is not reached by standard oral dosage forms in the upper GI tract in vivo due to dilution, interference from luminal components, fast intestinal transit, and possible absorption of the PE per se. The PE-based formulations that have been assessed in clinical trials in either immediate-release or enteric-coated solid dosage forms produce low and variable oral BA due to these uncontrollable physiological factors. For PEs to appreciably increase intestinal permeability from oral dosage forms in vivo, strategies must facilitate co-presentation of PE and active agent at the epithelium for a sustained period at the required concentrations. Focusing on peptides as examples of a macromolecule class, we review physiological impediments to optimal luminal presentation, discuss the efficacy of current PE-based oral dosage forms, and suggest strategies that might be used to improve them., Competing Interests: Declaration of Competing Interest SM declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. DB declares that he consults on oral peptide delivery for Pharma and has current grants relating to the specific topic from Gattefosse Ltd and Enterprise Ireland., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

In a formulation, traces of peroxides in copovidone can impact the stability of drug substances that are prone to oxidation. The present study aimed to investigate the impact of peroxides in novel Plasdone™ S630 Ultra and compare it with regular Plasdone™ S630 on the oxidative degradation of quetiapine fumarate amorphous solid dispersions prepared via hot-melt extrusion technique. The miscibility of copovidones with drug was determined using the Hansen solubility parameter, and the results indicated a miscible drug-polymer system. Melt viscosity as a function of temperature was determined for the drug-polymer physical mixture to identify the suitable hot-melt extrusion processing temperature. The binary drug and polymer (30:70 weight ratio) amorphous solid dispersions were prepared at a processing temperature of 160°C. Differential scanning calorimetry and Fourier transform infrared spectroscopy studies of amorphous solid dispersions revealed the formation of a single-phase amorphous system with intermolecular hydrogen bonding between the drug and polymer. The milled extrudates were compressed into tablets by using extragranular components and evaluated for tabletability. Stability studies of the milled extrudates and tablet formulations were performed to monitor the oxidative degradation impurity (N-oxide). The N-oxide impurity levels in the quetiapine fumarate - Plasdone™ S630 Ultra milled extrudates and tablet formulations were reduced by 2- and 3-folds, respectively, compared to those in quetiapine fumarate - Plasdone™ S630. The reduced oxidative degradation and improved hot-melt extrusion processability of Plasdone™ S630 Ultra make it a better choice for oxidation-labile drugs over Plasdone™ S630 copovidone.

In Belgium, the incorporation of phages into magistral preparations for human application has been permitted since 2018. The stability of such preparations is of high importance to guarantee quality and efficacy throughout treatments. We evaluated the ability to preserve infectivity of four different phages active against three different bacterial species in five different buffer and infusion solutions commonly used in medicine and biotechnological manufacturing processes, at two different concentrations (9 and 7 log pfu/mL), stored at 4 °C. DPBS without Ca 2+ and Mg 2+ was found to be the best option, compared to the other solutions. Suspensions with phage concentrations of 7 log pfu/mL were unsuited as their activity dropped below the effective therapeutic dose (6-9 log pfu/mL), even after one week of storage at 4 °C. Strong variability between phages was observed, with Acinetobacter baumannii phage Acibel004 being stable in four out of five different solutions. We also studied the long term storage of lyophilized staphylococcal phage ISP, and found that the titer could be preserved during a period of almost 8 years when sucrose and trehalose were used as stabilizers. After rehydration of the lyophilized ISP phage in saline, the phage solutions remained stable at 4 °C during a period of 126 days.

Purpose: A multitude of different versions of the same medication with different inactive ingredients are currently available. It has not been quantified how this has evolved historically. Furthermore, it is unknown whether healthcare professionals consider the inactive ingredient portion when prescribing medications to patients., Methods: We used data mining to track the number of available formulations for the same medication over time and correlate the number of available versions in 2019 to the number of manufacturers, the years since first approval, and the number of prescriptions. A focused survey among healthcare professionals was conducted to query their consideration of the inactive ingredient portion of a medication when writing prescriptions., Results: The number of available versions of a single medication have dramatically increased in the last 40 years. The number of available, different versions of medications are largely determined by the number of manufacturers producing this medication. Healthcare providers commonly do not consider the inactive ingredient portion when prescribing a medication., Conclusions: A multitude of available versions of the same medications provides a potentially under-recognized opportunity to prescribe the most suitable formulation to a patient as a step towards personalized medicine and mitigate potential adverse events from inactive ingredients.

Background: Bowel preparation for colonoscopy is often poorly tolerated due to poor palatability and adverse effects. This can negatively impact on the patient experience and on the quality of bowel preparation. This systematic review and meta-analysis was carried out to assess whether adjuncts to bowel preparation affected palatability, tolerability and quality of bowel preparation (bowel cleanliness)., Methods: A systematic search strategy was conducted on PubMed, MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews to identify studies evaluating adjunct use for colonoscopic bowel preparation. Studies comparing different regimens and volumes were excluded. Specific outcomes studied included palatability (taste), willingness to repeat bowel preparation, gastrointestinal adverse events and the quality of bowel preparation. Data across studies were pooled using a random-effects model and heterogeneity assessed using I 2 -statistics., Results: Of 467 studies screened, six were included for analysis (all single-blind randomised trials; n  = 1187 patients). Adjuncts comprised citrus reticulata peel, orange juice, menthol candy drops, simethicone, Coke Zero and sugar-free chewing gum. Overall, adjunct use was associated with improved palatability (mean difference 0.62, 95% confidence interval 0.29-0.96, p  < 0.001) on a scale of 0-5, acceptability of taste (odds ratio 2.75, 95% confidence interval: 1.52-4.95, p  < 0.001) and willingness to repeat bowel preparation (odds ratio 2.92, 95% confidence interval: 1.97-4.35, p  < 0.001). Patients in the adjunct group reported lower rates of bloating (odds ratio 0.48, 95% confidence interval: 0.29-0.77, p  = 0.003) and vomiting (odds ratio 0.47, 95% confidence interval 0.27-0.81, p  = 0.007), but no difference in nausea ( p  = 0.10) or abdominal pain ( p  = 0.62). Adjunct use resulted in superior bowel cleanliness (odds ratio 2.52, 95% confidence interval: 1.31-4.85, p  = 0.006). Heterogeneity varied across outcomes, ranging from 0% (vomiting) to 81% (palatability), without evidence of publication bias. The overall quality of evidence was rated moderate., Conclusion: In this meta-analysis, the use of adjuncts was associated with better palatability, less vomiting and bloating, willingness to repeat bowel preparation and superior quality of bowel preparation. The addition of adjuncts to bowel preparation may improve outcomes of colonoscopy and the overall patient experience.

Background: Medication self-management capacity (MMC) is essential to safe and independent living. There is a need to understand the challenges low-income older adults face during the routine use of medications to promote safe medication use and healthy aging in place., Objective: To assess the cognitive and physical deficiencies in MMC and the impact of using pharmaceutical aids/services on MMC among low-income older adults., Methods: This was a cross-sectional study of 107 older residents of 5 low-income housing buildings in Richmond, VA. The Medication Management Instrument for Deficiencies in the Elderly was used to measure MMC during individual in-person interviews. Participants were asked whether they used any medication aids, including medication lists, organizers, or reminders, or pharmacy services such as specialized medication packaging, medication synchronization, prescription home delivery, or mail order services. Multiple regression modeling was used to assess the relationship between MMC and the use of pharmaceutical aids/services., Results: Eighty-nine percent of participants were African American with a mean (standard deviation [±SD]) age of 68.5 (7.2) years. The mean deficit in MMC was 3 (±2.0). The most challenging skill was naming all the medications (69.2%), followed by stating their indications (46.7%) and knowing how or when all of the medications should be taken (38.3%). Seventy-nine percent used at least 1 pharmaceutical aid/service; using 1 pharmaceutical aid/service was significantly associated with better MMC (P = .0285). Low educational level and health literacy were associated with deficits in MMC (P < .05)., Conclusion: Many older adults residing in low-income housing had impaired capacity to manage their medications independently. Inadequate medication knowledge affected their cognitive ability to manage medications. Using a pharmaceutical aid/service was associated with better MMC. Greater attention to developing medication self-management skills for older adults with low health literacy and adverse social determinants of health is needed., Competing Interests: Disclosure The authors declare no relevant conflicts of interest or financial relationships., (Copyright © 2023 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Skin penetration/permeation enhancers are compounds that improve (trans)dermal drug delivery. We designed hybrid terpene-amino acid enhancers by conjugating natural terpenes (citronellol, geraniol, nerol, farnesol, linalool, perillyl alcohol, menthol, borneol, carveol) or cinnamyl alcohol with 6-(dimethylamino)hexanoic acid through a biodegradable ester linker. The compounds were screened for their ability to increase the delivery of theophylline and hydrocortisone through and into human skin ex vivo. The citronellyl, bornyl and cinnamyl esters showed exceptional permeation-enhancing properties (enhancement ratios up to 82) while having low cellular toxicities. The barrier function of enhancer-treated skin (assessed by transepidermal water loss and electrical impedance) recovered within 24 h. Infrared spectroscopy suggested that these esters fluidized the stratum corneum lipids. Furthermore, the citronellyl ester increased the epidermal concentration of topically applied cidofovir, which is a potent antiviral and anticancer drug, by 15-fold. In conclusion, citronellyl 6-(dimethylamino)hexanoate is an outstanding enhancer with an advantageous combination of properties, which may improve the delivery of drugs that have a limited ability to cross biological barriers.

Poly(2-ethyl-2-oxazoline) (PEOX), a biocompatible polymer considered as pseudopolypeptide, was introduced as a potential alternative to the commonly used polymer, poly(vinylpyrrolidone) (PVP) for the preparation of solid dispersion with a poorly soluble drug. Glipizide (GPZ), a Biopharmaceutical Classification System class II model drug, was selected for solubility and dissolution rate study. GPZ-polymer solid dispersions and physical mixtures were characterized and investigated by X-ray diffractometry, differential scanning calorimetry, scanning electron microscopy, and FTIR spectroscopy. The impact of polymers on crystal nucleation kinetics was studied, and PEOX exhibited strong inhibitory effect compared with PVP. Solubility and dissolution behavior of the prepared solid dispersions and their physical blends were in vitro examined and evaluated. A significant enhancement in GPZ solubility was obtained with PEOX compared with the pure drug and solid dispersion with PVP. A big improvement in the intrinsic dissolution rate (45 times) and dissolved amount of GPZ (58 times) was achieved with PEOX in fasted state simulated intestinal fluid, against comparable enhancement observed with PEOX and PVP in phosphate buffer at pH 6.8. Lower molecular weight of PEOX-5K (5000 g/mol) was found to be superior to higher molecular weight PEOX-50K (50,000 g/mol) in the improvement of dissolution behavior. The findings of this study with GPZ as a model drug introduce lower molecular weight PEOX as a promising polymeric carrier toward better oral bioavailability of poorly soluble drugs., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

From April 2001 to December 2002, a group of 514 patients (178 men, 336 women, average age 42.8 years) suffering from chronic eczema were tested by means of epicutaneous tests for contact hypersensitivity to selected auxiliary substances of dermatological external and cosmetic preparations. In 194 patients, the principal diagnosis was atopic eczema. Of the preservatives, the most frequently sensitizing agents were Thiomersal in 13.6%, phenylmercuric acetate in 7.8%, formaldehyde in 5.6%, Bronopol in 5.1%, chlorohexidine in 3.3%, dibromodicyanobutane/phenoxyethanol in 2.9%, chloroacetamide in 2.1%, Kathon CG and parabenes in 1.9%, imidazolidinyl urea and diazolidinyl urea in 1.4%, glutaraldehyde in 1.2%, DMDM-hydantoin in 1.0%, dichlorophen in 0.8%, sorbic acid, phenoxyethanol and triclosan in 0.6%, benzalkonium chloride, Quaternium-15 and chlorocresol in 0.4% and chloroquinaldol in 0.2% of the group of patients. Of antioxidizing agents, it was dodecyl gallate in 2.3%, butylhydroxyanisol in 1.2%, propyl gallate in 0.6%, butylhydroxytoluen in 0.4% of the group o patients and of emulsifiers, alcohols lanae in 5.1%, triethanolamine in 1.6% and propylene glycol in 0.4% of the group of patients. A complete list of contained substances in drug information sheets of both pharmaceutical and cosmetic preparations seems necessary particularly for patients suffering from eczema. The results of the test can serve as feed-back information for the manufacturers of both pharmaceutical and cosmetic preparations.

X-ray fluorescence analysis (XRF) has been employed for the identification and determination of elements with Z > 18. In pharmacy, it can be used to determine the content of elements in drugs and pharmaceutical auxiliary substances. The method makes it possible to distinguish heavy metals in the tests of purity of drugs. It can also be used to verify the origin of the raw material or drug on the basis of its elemental composition. The present paper is concerned with the preparation of samples of pharmaceutical auxiliary substances for the determination of the content of the elements Fe, Cu, Zn, and Pb by the XRF method with the use of a radionuclide source of 238Pu. For the determination of the content of elements, three kinds of standards were prepared aiming to remove the effect of absorption properties of the sample. The results with statistical evaluations of precision of measurement are tabulated. The study carried out an analysis of 7 samples of fillers, 3 samples of gelatine, 2 samples of SILOXID, and 1 sample of AEROSIL.

Effective solubilizers for poorly water-soluble active pharmaceutical ingredients (APIs) are highly desirable. This study introduced an amphiphilic dendrimer-like biopolymer, octenylsuccinate hydroxypropyl phytoglycogen (OHPP) as a new solubilizer. The molar substitution degree of octenylsuccinate and hydroxypropyl groups of OHPP was 0.51 and 1.69, respectively. The weight-average molecular weight, Z-average root mean square radius, and Zeta-potential of OHPP were 1.507×10 7 g/mol, 22.6nm, and -23.6mV, respectively. OHPP was highly soluble in polar organic solvents and aqueous buffers with pH≥5.0. To evaluate its solubilization capability, each of five APIs (celecoxib, docetaxel, fenofibrate, griseofulvin, and resveratrol) was incorporated with OHPP to form solid dispersions (API-OHPP SD). API-OHPP SD reduced API crystallinity and increased API solubility by up to 1755 times. Over the 3h dissolution, the cumulative dissolved API with API-OHPP SD was in the range of 6.8∼84.9%. Evidently, OHPP was a potent and non-specific polymeric solubilizer of poorly water-soluble APIs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

When gidazepam was administered to rats in combination with 4% solutions of Tween 80 or polyvinylpyrrolidone, its bioavailability was higher than its combination with 4% polyethylene glycol 400 solution, as shown by high performance liquid chromatography. Increasing the quantities of these high-molecular compounds in gidazepam solutions was demonstrated to enhance gidazepam dealkylation in the animals after oral administration.

Aim: The formulation of sustained release tablets of AMD-HCl using KOLLIDON SR as matrix-forming agent. Chitosan, a natural polysaccharide with superior hydrating and absorbing properties was used in the formulation stage to optimize the release characteristics of those matrix tablets., Material and Methods: Nine formulations of sustained release matrix tablets of AMD x HCl (200 mg/tablet) were prepared through direct compression. The concentrations of matrix forming agents were included as independent variables of a type 2(3) mixed factorial plan in order to develop formulations of AMD-HCl with optimal release characteristics. The dependent variables of that plan were the amount of AMD released from the tablets studied by using in vitro dissolution testing. The test was carried out in the paddle apparatus II for 12 hours in two pH media that were relevant to oral delivery: 2 hours at pH 1.2 and 10 hours at pH 6.8. The released AMD-HCl was quantitatively determined through a validated HPLC method., Results: The increase in KOL concentration leads to a decrease in AMD release rate at both pH values. The use of CHT resulted in a decrease of AMD release only at pH 6.8 in formulations with the lowest concentration of KOL., Conclusions: The retarding effect on the release of AMD-HCl in the tablets developed in this study was directly proportional to the KOL concentration in the formulation.

Pharmacists are required to ensure the quality of services provided to each patient. Good Pharmacy Practice (GPP) is a tool of clarifying and fulfilling this commitment. The role of International Pharmaceutical Federation (FIP) is to guide the national pharmaceutical organizations, which, in turn, should initiate the establishment of national standards. A key element is the obligation imposed by the profession throughout the world - to promote different activities for the benefit of those we serve. GPP is recommended to be considered as a list of occupational tasks, the implementation of which would serve the interests of patients or customers in the pharmacy. Ultimately, the quality of pharmaceutical care system will help to ensure not only the commercial interests of the pharmacy, but also the security requirements as those services and products, as well as professionals and patients.

A surface-attached silymarin-loaded solid dispersion with improved dissolution profile and enhanced oral bioavailability was formulated using silymarin, polyvinylpyrrolidone (PVP) and Tween 80 in water. In this solid dispersion, hydrophilic PVP was adhered onto the surface of crystalline drug rendering silymarin hydrophilic without changing its crystallinity. The drug solubility from the optimised solid dispersion prepared with silymarin/PVP/Tween 80 at the weight ratio of 5/2.5/2.5 increased by almost 650-fold compared to drug powder. The drug was physically and chemically stable in the solid dispersion for at least 6 months. Moreover, the solid dispersion enhanced the oral bioavailability of the drug in rats by almost 3-fold compared to the commercial product. The silymarin-loaded solid dispersion also exhibited advanced hepatoprotective bioactivity against CCl4-induced liver damage compared to silymarin or the commercial product. Thus, this silymarin-loaded solid dispersion would be useful for the enhancement of oral bioavailability and hepatoprotective activity of poorly water-soluble silymarin.

Silver nanoparticles (AgNPs) are increasingly applied to a wide range of materials for biomedical use. These enable a close contact with human skin, thanks to the large release of silver ions that is responsible for a broad spectrum of antimicrobial activity. Silver can permeate the skin; however, there are no data available on silver permeation through skin grafts commonly used in burns recovery. The aim of our study was to evaluate silver penetration using fresh, cryopreserved, and glycerolized human skin grafts after exposure to a suspension of AgNPs in synthetic sweat using a Franz diffusion cell apparatus for 24 h. Silver permeation profiles revealed a significantly higher permeation through glycerolized skin compared with both fresh and cryopreserved skin: 24-h silver flux penetration was 0.2 ng cm(-2) h(-1) (lag time: 8.2 h) for fresh skin, 0.3 ng cm(-2) h(-1) (lag time: 10.9 h) for cryopreserved skin, and 3.8 ng cm(-2) h(-1) (lag time: 6.3 h) for glycerolized skin. Permeation through glycerolized skin is significantly higher compared to both fresh and cryopreserved skin. This result can generate relevant clinical implications for burns treatment with products containing AgNPs., (Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.)

Background: Diseases of the bowel are not always displayed on conventional abdominal computed tomography (CT). The studied oral contrast agent aims to improve this., Purpose: To investigate whether the use of a novel oral contrast for abdominal CT enables the same diagnostic advantages as seen in magnetic resonance imaging (MRI)., Material and Methods: Twenty-five consented volunteers drank up to 1400 mL of a stable, drinkable foam. Comments on acceptance and side effects were noted immediately and 24 h later. Foam palatability was documented through interviews, and distribution in the small bowel by Hounsfield units from the CT software. The CT results were compared with age- and sex-matched controls, pretreated according to routine. A non-enhanced abdominal CT protocol of lowest possible radiation dose was used. External referees evaluated all data obtained., Results: Foam was considered odd to swallow, and fullness was reported by all volunteers after 950 mL. Five had difficulties in drinking the last 320 mL and two abstained from it. All adverse symptoms were mild. The distribution in the small bowel was on par with standard agents. Foam density revealed stability with intraluminal values of around -550 HU from stomach to terminal ileum, satisfying the requirement of a great bowel lumen-to-wall contrast. External reviewers re-evaluated all our data, and one predicted the foam to offer a potential for improved diagnostics., Conclusion: A CT true-negative bowel filling agent was formulated, with high acceptance, few side effects, and a potential to mimic T1-weighted MRI images.

Objective: To prepare Zhongjiefeng dispersible tablets., Methods: The formulation of Zhongjiefeng dispersible tablets were optimized as index of disintegration time by orthogonal design test., Results: The optimized Zhongjiefeng dispersible tablets, which were prepared by selecting 16% PVPP and 3% L-HPC as disintegrants, 40% MCC as filler, can disintegrate in 3 mins., Conclusions: The above formulation is reasonable and the disintegration time is suitable, so it can provide theoretic support for industrialization.

Room temperature ionic liquids (RTILs) are organic salts which are liquids at ambient temperature. Composed of relatively large asymmetric organic cations and inorganic or organic anions, they have generated interest as 'green' solvents. Here we report on the solvency of alkyl imidazolium salts (PF(6)(-)Br(-)Cl(-)) for poorly water-soluble model drugs, albendazole and danazol, indicating their potential application as pharmaceutical solvents/cosolvents. The solubility of albendazole, for example, is increased by more than 10,000 times by 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim]PF(6)(-)). Ionic liquids can be water-miscible or water-immiscible. The aqueous miscibility of a poorly water-miscible RTIL such as of [bmim]PF(6)(-) can be improved by the inclusion of a second more miscible RTIL (e.g. 1-hexyl-3-methylimidazolium bromide ([hmim]Br(-))). The extent of improvement in water miscibility was found to correlate with the hydrophilicity of the second RTIL. This ability to modulate RTILs' aqueous miscibility increases their usefulness as pharmaceutical solvents.