Locked posterior shoulder dislocations are dislocations that remain unreduced for more than three weeks. In most cases, they are associated with other injuries. We report the case of a 38-year-old male who presented with pain and total functional impotence due to a complex injury, including posterior glenohumeral dislocation, a reverse Hill-Sachs lesion, and a clavicle fracture.
View Article and Find Full Text PDFThe single-bone forearm is a salvage technique for massive loss of bone due to serious trauma, malignant tumors, infections or congenital deformity. It is also described to treat the sequelae of hereditary multiple exostoses disease that affects the distal end of the ulna. We present the case of a 29-year-old patient, operated for sequelae of hereditary multiple exostoses disease of the left forearm by a modified single-bone forearm technique.
View Article and Find Full Text PDFPurpose: The use of ionic liquids (ILs) in drug delivery has focused attention on non-toxic IL counterions. Cationic lipids can be used to form ILs with weakly acidic drugs to enhance drug loading in lipid-based formulations (LBFs). However, cationic lipids are typically toxic.
View Article and Find Full Text PDFType III lipid-based formulations (LBFs) combine poorly water-soluble drugs with oils, surfactants, and cosolvents to deliver the drugs into the systemic circulation. However, the solubility of the drug can be influenced by the colloidal phases formed in the gastrointestinal tract as the formulation is dispersed and makes contact with bile and other materials present within the GI tract. Thus, an understanding of the phase behavior of LBFs in the gut is critical for designing efficient LBFs.
View Article and Find Full Text PDFObjective: Molecular dynamics (MD) simulations provide an in silico method to study the structure of lipid-based formulations (LBFs) and the incorporation of poorly water-soluble drugs within such formulations. In order to validate the ability of MD to effectively model the properties of LBFs, this work investigates the well-known cyclosporine A formulations, Sandimmune® and Neoral®. Sandimmune® exhibits poor dispersibility and its absorption from the gastrointestinal tract is enhanced when administered after food, whereas Neoral® disperses comparatively well and shows no food effect.
View Article and Find Full Text PDFPurpose: Successful oral peptide delivery faces two major hurdles: low enzymatic stability in the gastro-intestinal lumen and poor intestinal membrane permeability. While lipid-based formulations (LBF) have the potential to overcome these barriers, effective formulation of peptides remains challenging. Lipophilic salt (LS) technology can increase the apparent lipophilicity of peptides, making them more suitable for LBF.
View Article and Find Full Text PDFTennis-leg is a partial or total disinsertion of the medial head of the gastrocnemius muscle from its musculoskeletal junction. Patients receiving adequate treatment generally have favorable outcome. Tennis leg is rarely associated with major complications such as acute compartment syndrome.
View Article and Find Full Text PDFSquamous cell carcinoma associated with chronic osteomyelitis is rare. However, it must be suspected in patients with modification of common local symptoms. Delayed diagnosis can be fatal.
View Article and Find Full Text PDFLipid based formulations (LBFs) can enhance oral bioavailability, however, their utility may be restricted by low drug loading in the formulation. Converting drugs to drug-ionic liquids (drug-ILs) or lipophilic salts can significantly increase lipid solubility but this approach is complicated in some cases by salt disproportionation, leading to a reduction in solubility and physical instability. Here we explore the physical stability of the weakly basic model drug, cinnarizine (CIN), when paired with a decanoate counterion (Dec) to form the drug-IL, cinnarizine decanoate (CIN.
View Article and Find Full Text PDFBone is the most transplanted human tissue. Surgical interventions for bone repair are necessary for various pathologies such as nonunion, osteoporosis or osteonecrosis. Although autologous bone grafts remain the benchmark for bone regeneration, they unfortunately have a number of disadvantages: the need for a second intervention and the limited amount of tissue removed.
View Article and Find Full Text PDFSchwannomas of the sciatic nerve are rare tumors. They are mainly manifested by sciatic neuralgia rather than by sensory-motor deficits. We report the case of a 30-year-old female patient with right buttock pain for 1 year.
View Article and Find Full Text PDFHypothesis: Non-ionic surfactants containing polyethylene oxide (PEO) chains are widely used in drug formulations, cosmetics, paints, textiles and detergents. High quality molecular dynamics models for PEO surfactants can give us detailed, atomic-scale information about the behavior of surfactant/water mixtures.
Simulations: We used two molecular dynamics force fields (FFs), 2016H66 and 53A6, to model the simple non-ionic PEO surfactant, hexaoxyethylene dodecyl ether (CE).
Lipid based formulations (LBFs) are extensively utilised as an enabling technology in drug delivery. The use of ionic liquids (ILs) or lipophilic salts (LS) in drug delivery has also garnered considerable interest due to unique solubility properties. Conversion of active pharmaceutical ingredients (API) to ILs by pairing with an appropriately lipophilic counterion has been shown to decrease melting point of the salt complex and improve solubility in LBFs.
View Article and Find Full Text PDFLipid based formulations (LBFs) are commonly employed to enhance the absorption of highly lipophilic, poorly water-soluble drugs. However, the utility of LBFs can be limited by low drug solubility in the formulation. Isolation of ionizable drugs as low melting, lipophilic salts or ionic liquids (ILs) provides one means to enhance drug solubility in LBFs.
View Article and Find Full Text PDFThe fasted state administration of immediate release (IR) dosage forms is often regarded as uncritical since physiological aspects seem to play a minor role for disintegration and drug release. However, recent in vivo studies in humans have highlighted that fasted state conditions are in fact highly dynamic. It was therefore the aim of this study to investigate the disintegration and drug release behavior of four different IR formulations of the probe drug caffeine under physiologically relevant conditions with the aid of the GastroDuo.
View Article and Find Full Text PDFThe instability of various small molecules, vaccines and peptides in the human stomach is a complex challenge for oral drug delivery. Recently, a novel gastro-resistant capsule - the enTRinsic™ Drug Delivery Technology capsule - has been developed. In this work, the salivary tracer technique based on caffeine has been applied to study the in vivo disintegration of enTRinsic™ capsules in 16 healthy volunteers.
View Article and Find Full Text PDFLipid-based formulations (LBF) are widely used by industry and accepted by the regulatory authorities for oral drug delivery in the pharmaceutical and consumer healthcare market. Innovation in the LBF field is however needed in order to meet the demands of modern drugs, their more challenging problem statements and growing needs for achieving optimal pharmacokinetics (i.e.
View Article and Find Full Text PDFThe application areas of hard capsules are currently widened by the introduction of acid-resistant capsule shells. In this study, the gastrointestinal behavior of acid-resistant hard capsule formulations as well as the influence of their density on the gastric residence time were characterized using magnetic resonance imaging (MRI). As labeling material for a reliable identification of the capsules in the MR images, small pieces of dried pineapple were used as they provide a high T1 signal.
View Article and Find Full Text PDFPolyethoxylated, nonionic surfactants are important constituents of many drug formulations, including lipid-based formulations. In an effort to better understand the behavior of formulation excipients at the molecular level, we have developed molecular dynamics (MD) models for the widely used surfactant Kolliphor EL (KOL), a triricinoleate ester of ethoxylated glycerol. In this work, we have developed models based on a single, representative molecular component modeled with 2 force field variations based on the GROMOS 53A6 and 2016H66 force field parameters for polyethoxylate chains.
View Article and Find Full Text PDFMolecular dynamics simulations can be applied to explore the complex liquid phase behavior of lipid-based formulations and the gastrointestinal tract lumen. In order for the results from these simulations to be of value, the manner in which molecules interact with both aqueous and oil phases present needs to be as correct as possible. An existing molecular dynamics force field, GROMOS 53a6, was demonstrated to poorly reproduce the partitioning of straight-chain alcohol and short-chain polyethylene glycol (PEG) molecules between octanol and water phase (logP), with the molecules too hydrophobic.
View Article and Find Full Text PDFAn iconic textbook that pharmaceutical scientists encounter in undergraduate courses is "Martin's Physical Pharmacy and Pharmaceutical Sciences." Within the chapter on Colloids, a figure indicates the location of solubilization of molecules within spherical, nonionic surfactant micelles. The surfactant consists of polyethylene glycol (PEG) hydrophilic headgroups and alkane chains for the hydrophobic tail.
View Article and Find Full Text PDFThe absolute bioavailability of many small molecule kinase inhibitors (smKIs) is low. The reasons for low bioavailability are multifaceted and include constraints due to first pass metabolism and poor absorption. For smKIs where absorption limits oral bioavailability, low aqueous solubility and high lipophilicity, often in combination with high-dose requirements have been implicated in low and variable absorption, food-effects, and absorption-related drug-drug interactions.
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