In this research, a novel composite material composed of Metal-Organic Framework material (MOF) and graphite oxide was synthesized and evaluated as a possible drug-loading vehicle. HKUST-1, a MOF material originally designed by the Hong Kong University of Science and Technology, was used as a model porous material. The aim was to synthesize a drug delivery vehicle for modifying the release kinetics and solubility of poorly soluble drugs (BSC Class II drugs); these are drugs that are known to have poor bioavailability due to their low solubility. We used ketoprofen, ibuprofen, and felodipine as models for BSC Class II drugs. The drugs were loaded onto composite materials through adsorption. The adsorption of these three drugs into the matrix of HKUST-1/GO (graphite oxide), HKUST-1, and graphite oxide was compared. The loading efficiency of the drugs onto the carrier was dependent on the drug molecule and the composition of the drug carrier. The inclusion of graphite oxide in the drug carrier matrix improved the drug loading capacity and modified the drug release rate. The loading of the three drugs felodipine, ketoprofen, and ibuprofen onto HKUST-1 were 33.7, 58, and 79 mg/g respectively. The incorporation of GO into the HKUST-1 matrix resulted in an increase in the loading by 16 and 4 mg/g for the ketoprofen and ibuprofen drugs. When compared to the pure drugs, the solubility of all three drugs in the HKUST-1/GO matrix increased by at least 6 folds.

Gingival enlargement may manifest as a side effect of medications (calcium channel blockers, anticonvulsants, or immunosuppressants) and may be associated with inflammation, malignancy, or genetic inheritance. This condition has a significant impact on a patient\'s quality of life and affects their oral health status. This case report describes the management of a 68-year-old gentleman who presented with generalized gingival enlargement and chronic periapical abscess originating from tooth 34, which served as an abutment for a fixed partial prosthesis. The patient\'s medical history revealed that felodipine, an antihypertensive medication, was prescribed to him. A comprehensive treatment plan was developed to improve the patient\'s quality of life.

OBJECTIVE: To test whether a side-by-side diffusion model is suitable for studying drug supersaturation in an absorptive environment.
METHODS: The µD/P model and the µFLUX model, using a Caco-2 cell monolayer/PAMPA membrane as the permeation barrier, respectively, were compared in terms of robustness and ease of handling, while studying the drug supersaturation-precipitation-permeation interplay. Continuing with the best model, the impact of the acceptor media and the importance of studying drug supersaturation in a combined dissolution-permeation model, as compared to a simple dissolution model, were evaluated.
RESULTS: The two models produced similar results in terms of supersaturation, precipitation and permeation. The µFLUX model was considered more robust and easier to handle based on its cell-free permeation system. Using the µFLUX model, it was found that an acceptor medium with a high surfactant concentration increased the amount of permeated drug. The effect of absorption on drug supersaturation was found to be dependent on the drug, and the tested level of supersaturation.
CONCLUSIONS: The tested models were comparable; however, Caco-2 cell monolayers were considered too sensitive to be used to study drug supersaturation. Further studies are needed to evaluate the observed drug-dependent effects of absorption on drug supersaturation.

Gingival overgrowth (GO) includes gingival enlargement and hyperplasia and may be induced by certain drugs, including calcium channel blockers (CCBs), particularly first-generation CCBs. However, to date, only few cases of GO induced by second- or third-generation CCBs have been reported. The present study reports on a case of a 48-year-old diabetic male who was admitted to the First Hospital of Jilin University (Changchun, China) due to poor blood glucose control. This patient was diagnosed with GO. Review of the patient\'s medical history revealed diagnoses of type 2 diabetes and hypertension, as well as the use of felodipine, a second-generation CCB, to control hypertension. The hypertensive drugs were replaced and the new drugs helped the patient control his blood glucose levels. Additionally, the patient was instructed on methods he could use to improve his oral hygiene, including rinsing of the teeth following each meal and increasing the frequency of tooth brushing per day. After 3 months, the clinical symptoms of GO were relieved. The relevant literature was also reviewed to gain an improved understanding of the correlation between GO and CCBs, as well as diabetes and poor oral hygiene.

Water is often readily absorbed by amorphous compounds, lowering their glass transition temperature (Tg) and facilitating their recrystallization (via nucleation-and-growth). At the same time, the increase in moisture content translates to a decrease in both the thermodynamic solubility and intrinsic dissolution rate, as compared to the corresponding dry (pure) amorphous phase, e.g. see [Murdande SB, Pikal MJ, Shanker RM, Bogner RH. 2010. Solubility advantage of amorphous pharmaceuticals: I. A thermodynamic analysis. J Pharm Sci 99:1254-1264.]. In the case of pure indomethacin and felodipine, the solubility advantage of each amorphous phase over its crystalline counterpart were previously determined to be 7.6 and 4.7, respectively, using a new methodology together with basic calorimetric data taken from the literature. Herein, we demonstrate that, theoretically, following the uptake of just ∼0.5% w/w water, the solubility ratios decrease to 6.9 and 4.5, in the same order. Moreover, as the predicted intrinsic dissolution rate (based on the Noyes-Whitney equation) is directly proportional to the solubility advantage of a given amorphous-crystalline pair, it decreases proportionately upon moisture uptake. Applying the methodology presented herein, one can directly predict the extent of Tg-lowering observed at any moisture content, for a given amorphous phase. Knowing that value, it is possible to estimate the relative decrease in the solubility and/or intrinsic dissolution rate of the plasticized phase compared to the pure glass, and vice-versa.

Because of health benefits that are manifested across various disease areas, the consumption of herbal products and/or health supplements containing different kinds of flavonoids has been on the rise. While the drug-drug interaction potential between flavonoids and co-ingested drugs still remain an issue, opportunities exist for the combination of flavonoids with suitable anti-cancer drugs to enhance the bioavailability of anti-cancer drugs and thereby reduce the dose size of the anti-cancer drugs and improve its therapeutic index. In recent years, scores of flavonoids have undergone preclinical investigation with variety of drugs encompassing therapeutic areas such as oncology (etoposide, doxorubicin, paclitaxel, tamoxifen etc.), immunosuppression (cyclosporine) and hypertension (losartan, felodipine, nitrendipine etc.). The review provides examples of the recent trends in the preclinical investigation of 14 flavonoids (morin, quercetin, silibinin, kaempferol etc.) with various co-administered drugs. The relevance of combination of flavonoids with anti-cancer drugs and a framework to help design the in vitro and in vivo preclinical studies to gain better mechanistic insights are discussed. Also, concise discussions on the various physiological factors that contribute for the reduced bioavailability of flavonoids along with the significant challenges in the data interpretation are provided.

\"Gingival enlargement\" is the term now used to describe medication-related gingival overgrowth or gingival hyperplasia (AAP, 2004), a condition commonly induced by three main classes of drugs: anticonvulsants, antihypertensive calcium antagonists and the immunosuppressant cyclosporin. It is important that the health practitioner is aware of the potential aetiologic agents and characteristic features in order to be able to accurately diagnose and successfully manage patients who present with a condition such as outlined in the following case presentation.

The case of a 51-year-old man who ingested 100 mg of felodipine (Plendil, 20 tablets á 5 mg) and 9 g of theophylline (Theospirex retard, 30 tablets á 300 mg) is presented. The patient developed severe hypotension, tachycardia, circulatory insufficiency and paralytic ileus. No ECG effects were observed. Although felodipine led to a reduction in the bioability of theophylline, the serum theophylline concentration 15 h after the admission was 92 mg/L (the therapeutic concentration of theophylline 10-20 mg/L). The protracted hypotension did not respond to vasopressor and calcium therapy. The addition of 4-aminopyridine (4-AP) infusion resulted in fast receding of poisoning symptoms: increase of blood pressure, receding of circulatory insufficiency and metabolic acidosis, and return of peristalsis. This case suggests the usefulness of 4-AP in the treatment of poisoning by dihydropyridine derivatives. However, confirmation of the effectiveness of this substance for pharmacotherapy of dihydrophyridine derivatives poisoning requires further clinical research. The influence of 4-AP on calcium channels is indirect. It blocks potassium channels K1 in cytoplasm side which makes potassium stay inside the cell leading to depolarisation and opening of voltage-dependent calcium channels.

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A 28-year-old woman with end-stage renal disease secondary to diabetes mellitus and hypertension underwent cadaver renal transplant in April 1992. After surgery, she developed bilateral breast enlargement while she was taking cyclosporine for immunosuppression therapy and felodipine, a calcium channel blocker, for blood pressure control. She underwent bilateral reduction mammoplasty in June 1995 to treat progressive breast enlargement which interfered with her normal life activities. Through mechanisms only partially understood, calcium channel blockers and cyclosporine are reported to increase the serum prolactin level, producing gynecomastia in men. There is no report in current literature to support a similar phenomenon in women.