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Nutrition, Metabolism, and... Feb 2021The oral administration of insulin has so far been precluded by gastro-intestinal enzyme degradation and poor intestinal absorption. Preliminary evidence for peptide...
BACKGROUND AND AIMS
The oral administration of insulin has so far been precluded by gastro-intestinal enzyme degradation and poor intestinal absorption. Preliminary evidence for peptide uptake by the gut has recently been obtained, by our research group, following the administration of nanostructured lipid-carrier suspensions loaded with glargine insulin in healthy animal models.
METHODS AND RESULTS
In this experimental study, glargine insulin-loaded nanostructured lipid carriers have been converted into solid oral dosage forms (tablets, capsules), that are more suitable for administration in humans and have prolonged shelf-life. The liquid and solid oral dosage forms were tested for glargine insulin uptake and glucose responsivity in healthy and streptozotocin-induced diabetic rats (6 animals in each group). A suitable composition gave redispersible solid oral dosage forms from glargine insulin-loaded carriers, using both spray-drying and freeze-drying. It was observed that the liquid and solid formulations had relevant hypoglycaemic effects in healthy rats, while only capsules were efficacious in diabetic rats; probably because of gut alterations in these animal models. Detected glargine insulinaemia was consistent with a glycaemic profile.
CONCLUSION
The formulations under study showed their potential as oral glucose-lowering agents, particularly when used as capsules. However, further study is needed to produce a useful orally-active insulin preparation.
Topics: Administration, Oral; Animals; Biomarkers; Blood Glucose; Capsules; Diabetes Mellitus, Experimental; Drug Carriers; Drug Compounding; Hypoglycemic Agents; Insulin Glargine; Lipids; Male; Nanoparticles; Pharmaceutical Solutions; Rats, Wistar; Streptozocin; Tablets; Rats
PubMed: 33131992
DOI: 10.1016/j.numecd.2020.09.020 -
Current Opinion in Pharmacology Jun 2018Intra-articular (IA) injections directly deliver high concentrations of therapeutics to the joint space and are routinely used in various musculoskeletal conditions such... (Review)
Review
Intra-articular (IA) injections directly deliver high concentrations of therapeutics to the joint space and are routinely used in various musculoskeletal conditions such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, current IA-injected drugs are rapidly cleared and do not significantly affect the course of joint disease. In this review, we highlight recent developments in IA therapy, with a special emphasis on current and emerging therapeutic carriers and their potential to deliver disease-modifying treatment modalities for arthritis. Recent IA approaches concentrate on platforms that are safe with efficient tissue penetration, and readily translatable for controlled and sustained delivery of therapeutic agents. Gene therapy delivered by viral or non-viral vectors and cell-based therapy for cartilage preservation and regeneration are being intensively explored.
Topics: Animals; Antirheumatic Agents; Delayed-Action Preparations; Dosage Forms; Drug Carriers; Drug Compounding; Drug Development; Drug Discovery; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; Injections, Intra-Articular; Joint Diseases; Joints
PubMed: 29625332
DOI: 10.1016/j.coph.2018.03.013 -
Advanced Drug Delivery Reviews Oct 2021The use of chemical permeation enhancers (PEs) is the most widely tested approach to improve oral absorption of low permeability active agents, as represented by... (Review)
Review
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.
Topics: Animals; Dosage Forms; Drug Compounding; Drug Delivery Systems; Food-Drug Interactions; Humans; Intestinal Absorption; Permeability; Pharmaceutic Aids
PubMed: 34418495
DOI: 10.1016/j.addr.2021.113925 -
Chemical & Pharmaceutical Bulletin 2020The dosages of drugs in newborn infants are small. Small dose necessitate consideration of the loss of drug when administered via feeding tube. In this study, we...
The dosages of drugs in newborn infants are small. Small dose necessitate consideration of the loss of drug when administered via feeding tube. In this study, we conducted a tube administration test for seven kinds of antiepileptic drugs and two kinds of potassium supplements using a neonatal feeding tube and investigated the drug loss using the collection rate. We also studied the differences in collection rates among different dosage forms and drugs to determine the more suitable dosage forms and drugs. We investigated three dosage forms: powder, fine granules or dry syrup (powdery form) drugs, powdery form drugs that have been pulverized (pulverized powdery forms), and pulverized tablets. Additionally, we investigated two potassium supplements to determine which was more suitable: potassium L-aspartate and potassium gluconate. For topiramate, only the powdery form caused tube obstructions; the collection rates of the pulverized powdery form and pulverized tablets were > 90%. All antiepileptic drugs other than topiramate that were tested had collection rates of about > 90%. Considering stability and pharmacokinetics, the more suitable dosage form for topiramate is pulverized tablets, whereas the more suitable dosage form for other antiepileptic drugs is powdery form. Collection rate of potassium gluconate was higher than that of potassium L-aspartate. The current study, which indicates that potassium gluconate powdery form is the more suitable drug, presents the more suitable dosage form and drug for administration via feeding tube to newborn infants. These results show that it is essential to evaluate passage through the tube using the collection rate.
Topics: Anticonvulsants; Aspartic Acid; Dietary Supplements; Enteral Nutrition; Humans; Infant, Newborn; Potassium; Powders; Tablets; Temperature
PubMed: 32741923
DOI: 10.1248/cpb.c20-00154 -
International Journal of Pharmaceutics Nov 2022The high degree of precision and control of 3D printing has given formulators the autonomy to engineer sophisticated and personalised medicines, starting a revolution in... (Review)
Review
The high degree of precision and control of 3D printing has given formulators the autonomy to engineer sophisticated and personalised medicines, starting a revolution in pharmaceutics. In addition, dosage forms with tailored drug release profile can be produced by changing some parameters of the 3D printing processes. Therefore, 3D printed medicines must be characterised in an orthogonal approach, to establish their physicochemical and biopharmaceutical features, and consequently to understand how these characteristics can be customised by changing the formulation and process parameters to ensure medicines' safety and efficacy. Given the recent regulation and commercialisation of 3D printed medicines, several methods and techniques have been transposed from official compendia; however, formulators must still make a critical assessment of their practical implications. A comprehensive review of the findings obtained by the characterisation of 3D printed oral dosage forms using traditional and advanced techniques is therefore presented here, to drive formulators towards a rational pharmaceutical development pathway. The characterisation methods have been classified in terms of their physicochemical or biopharmaceutical character. Interestingly, beyond the rise of modern characterisation techniques, the reassessment of data obtained by traditional methods has provided knowledge and a solid foundation to support the evolution of 3D printing techniques in pharmaceutics.
Topics: Technology, Pharmaceutical; Drug Liberation; Printing, Three-Dimensional; Biological Products; Dosage Forms
PubMed: 36252640
DOI: 10.1016/j.ijpharm.2022.122293 -
Marine Drugs Dec 2022Alginates (ALG) have been used in biomedical and pharmaceutical technologies for decades. ALG are natural polymers occurring in brown algae and feature multiple... (Review)
Review
Alginates (ALG) have been used in biomedical and pharmaceutical technologies for decades. ALG are natural polymers occurring in brown algae and feature multiple advantages, including biocompatibility, low toxicity and mucoadhesiveness. Moreover, ALG demonstrate biological activities per se, including anti-hyperlipidemic, antimicrobial, anti-reflux, immunomodulatory or anti-inflammatory activities. ALG are characterized by gelling ability, one of the most frequently utilized properties in the drug form design. ALG have numerous applications in pharmaceutical technology that include micro- and nanoparticles, tablets, mucoadhesive dosage forms, wound dressings and films. However, there are some shortcomings, which impede the development of modified-release dosage forms or formulations with adequate mechanical strength based on pure ALG. Other natural polymers combined with ALG create great potential as drug carriers, improving limitations of ALG matrices. Therefore, in this paper, ALG blends with pectins, chitosan, gelatin, and carrageenans were critically reviewed.
Topics: Alginates; Drug Delivery Systems; Polymers; Drug Carriers; Chitosan
PubMed: 36662184
DOI: 10.3390/md21010011 -
British Journal of Clinical Pharmacology Jun 2005The development of age-adapted dosage forms and taste-masking of bitter-tasting drugs administered orally for children, are formidable challenges for formulation... (Review)
Review
The development of age-adapted dosage forms and taste-masking of bitter-tasting drugs administered orally for children, are formidable challenges for formulation scientists. Childhood is a period of maturation requiring knowledge of developmental pharmacology to establish dose but the ability of the child to manage different dosage forms and devices also changes. Paediatric formulations must allow accurate administration of the dose to children of widely varying age and weight. Whilst the oral route will be preferred for long term use and the intravenous route for the acutely ill, many of the dosage forms designed for adults, such as oro-dispersible tablets, buccal gels and transdermal patches, would also benefit children if they contained an appropriate paediatric dose. The age at which children can swallow conventional tablets is of great importance for their safety. Liquid medicines are usually recommended for infants and younger children so the ability to mask unpleasant taste with sweeteners and flavours is crucial. More sophisticated formulations such as granules and oro-dispersible tablets may be required but there will be limitations on choice and concentration of excipients. There are many gaps in our knowledge about paediatric formulations and many challenges for the industry if suitable preparations are to be available for all ranges. A CHMP points to consider document is soon to be released. More research and clinical feedback are important because a formulation with poor acceptability may affect compliance, prescribing practice and ultimately commercial viability.
Topics: Adolescent; Aging; Chemistry, Pharmaceutical; Child; Dosage Forms; Drug Delivery Systems; Humans; Patient Acceptance of Health Care
PubMed: 15948931
DOI: 10.1111/j.1365-2125.2005.02410.x -
Expert Opinion on Drug Delivery Feb 2021Nanocarrier-based delivery systems offer multiple benefits to overcome limitations of the traditional drug dosage forms, such as protection of the drug, enhanced... (Review)
Review
INTRODUCTION
Nanocarrier-based delivery systems offer multiple benefits to overcome limitations of the traditional drug dosage forms, such as protection of the drug, enhanced bioavailability, targeted delivery to disease site, etc. Nanocarriers have exhibited tremendous successes in targeted delivery of therapeutics to the desired tissues and cells with improved bioavailability, high drug loading capacity, enhanced intracellular delivery, and better therapeutic effect. A specific design of stimuli-responsive nanocarriers allows for changing their structural and physicochemical properties in response to exogenous and endogenous stimuli. These nanocarriers show a promise in site specific controlled release of therapeutics under certain physiological conditions or external stimuli.
AREAS COVERED
This review highlights recent progresses on the multifunctional and stimuli-sensitive nanocarriers for targeted therapeutic drug delivery applications.
EXPERT OPINION
The progress from single functional to multifunctional nanocarriers has shown tremendous potential for targeted delivery of therapeutics. On our opinion, the future of targeted delivery of drugs, nucleic acids, and other substances belongs to the site-targeted multifunctional and stimuli-based nanoparticles with controlled release. Targeting of nanocarriers to the disease site enhance the efficacy of the treatment by delivering more therapeutics specifically to the affected cells and substantially limiting adverse side effects upon healthy organs, tissues, and cells.
Topics: Drug Carriers; Drug Delivery Systems; Nanoparticles; Nucleic Acids
PubMed: 32969740
DOI: 10.1080/17425247.2021.1828339 -
Medecine Sciences : M/S Jan 2017Implants for controlled drug delivery can be very helpful to improve the therapeutic efficacy of a medical treatment, and at the same time reduce the risk of toxic side... (Review)
Review
Implants for controlled drug delivery can be very helpful to improve the therapeutic efficacy of a medical treatment, and at the same time reduce the risk of toxic side effects. In this article, four different strategies are exemplarily presented: hybrid bone substitutes combining hydroxyapatite and chitosan hydrogels; vascular stents coated with a bio-inspired polymer; cochlear implants for local dexamethasone delivery; and in-situ forming implants for periodontitis treatment. But this is only a restricted selection, and numerous other approaches and applications based on implants releasing a drug (or a combination of drugs) exist. Compared to conventional implants or pharmaceutical dosage forms, they might offer decisive advantages.
Topics: Animals; Cochlear Implants; Dental Implants; Drug Delivery Systems; Drug Implants; Drug-Eluting Stents; Graft Occlusion, Vascular; Humans; Periodontium; Polymers
PubMed: 28120753
DOI: 10.1051/medsci/20173301006 -
Drug Delivery Dec 2022Self-emulsifying drug delivery systems (SEDDS) are a proven method for poorly soluble substances works by increasing the solubility and bioavailability. SEDDS and... (Review)
Review
Self-emulsifying drug delivery systems (SEDDS) are a proven method for poorly soluble substances works by increasing the solubility and bioavailability. SEDDS and isotropic mixtures, are composed of oils, surfactants, and occasionally cosolvents. The ability of these formulations and methods to produce microemulsions or fine oil-in-water (o/w) emulsions after moderate stirring and dilution by water phase along the GI tract might be a promising technique for lipophilic agents with dissolution rate-limited absorption. This review provides an outline of SEDDS's numerous advances and biopharmaceutical elements, types, manufacturing, characterization, limitations, and future prospects. The evaluation of SEDDS and its applications are also discussed, focusing on the advances of SEDDS's solid self-emulsifying delivery mechanism and dosage form. By integrating suitable polymer into the formulation, SEDDS may be studied for the creation of a formulation with sustained drug release. This technology's improvement might lead to a new application in the field of medicine delivery. SEDDS has been demonstrated to be quite efficient in increasing oral bioavailability of lipophilic products. SEDDS is one of the promising methods for controlling the characteristics of medications that are not great choices for oral delivery. It is also worth mentioning that SEDDS may be made in variety of solid dosage forms that are acceptable for both oral and parenteral administration.
Topics: Administration, Oral; Biological Availability; Drug Delivery Systems; Emulsions; Solubility; Water
PubMed: 35666090
DOI: 10.1080/10717544.2022.2083724