Ocular pharmacokinetics of acetazolamide from intravitreal implants by high-performance liquid chromatography coupled to tandem mass spectrometry.

Glaucoma, a leading cause of irreversible blindness, affects about 70 million people globally. Its treatment focuses on reducing intraocular pressure. Acetazolamide, a potent anti-glaucoma drug, is currently used only systemically due to low solubility and permeation, which cause severe side effects.

Highly Soluble Dacarbazine Multicomponent Crystals Less Prone to Photodegradation.

Dacarbazine (DTIC) is a widely prescribed oncolytic agent to treat advanced malignant melanomas. Nevertheless, the drug is known for exhibiting low and pH-dependent solubility, in addition to being photosensitive. These features imply the formation of the inactive photodegradation product 2-azahypoxanthine (2-AZA) during pharmaceutical manufacturing and even drug administration.

Intravitreal acetazolamide implant for pseudophakic cystoid macular edema.

Background: Pseudophakic cystoid macular edema (PCME) is the most common cause of visual acuity deterioration after uncomplicated cataract surgery. There is no consensus regarding how to manage recurrent or refractory cases.

Report: A 54-year-old woman complained of decreased vision and central metamorphopsia in the right eye (OD) 3 months after uneventful cataract surgery.

Thermal energy and tableting effects in benznidazole product: the impacts of industrial processing.

Objective: The investigation of benznidazole (BZN), excipients, and tablets aims to evaluate their thermal energy and tableting effects. They aim to understand better the molecular and pharmaceutical processing techniques of the formulation.

Significance: The Product Quality Review, part of Good Manufacturing Practices, is essential to highlight trends and identify product and process improvements.

Tocotrienols-enriched Self-nanoemulsifying Drug Delivery System Enhances the Antileukemic Activity of All-trans Retinoic Acid but not Electrocardiogram Alterations Evoked by Its Combination with Arsenic Trioxide.

All-trans retinoic acid and arsenic trioxide are the leading choices for the treatment of acute promyelocytic leukemia. Notwithstanding the impressive differentiative properties of all-trans retinoic acid and the apoptotic properties of arsenic trioxide, some problems still occur in acute promyelocytic leukemia treatment. These problems are due to patients' relapses, mainly related to changes in the ligand-binding domain of RARα (retinoic acid receptor α) and the cardiotoxic effects caused by arsenic trioxide.

Microextraction by packed sorbent and high-performance liquid chromatography for determination of benznidazole in human plasma.

Benznidazole is the main drug used in Chagas disease and its determination in plasma samples is useful in several situations. Hence, robust and accurate bioanalytical methods are needed. In this context, sample preparation deserves special attention, as it is the most error-prone, labor-intensive and time-consuming step.

Thermoresponsive in-situ gel containing hyaluronic acid and indomethacin for the treatment of corneal chemical burn.

Ocular chemical burns are prevalent injuries that must have immediate and effective treatment to avoid complications. Aiming to improve bioavailability and efficacy, a poloxamer-based thermoresponsive in-situ gelling system containing hyaluronic acid and indomethacin was developed. Formulations with different polymeric proportions were screened through rheological measurements resulting in an optimized system (F2) with gelling temperature of 34.

Cholesterol improves stability of amphotericin B nanoemulsion: promising use in the treatment of cutaneous leishmaniasis.

Amphotericin B (AmB) is an antileishmanial drug with high toxicity; however, this drawback might overcome by decreasing the AmB self-aggregation state. This work aimed at evaluating the influence of cholesterol on the aggregation state of AmB loaded in a nanoemulsion (NE-AmB) for the treatment of cutaneous leishmaniasis. NE-AmB (1, 4 and 8 mg/kg/day) was administered intravenously to animals infected by every 2 days for a total of five injections.

Boron nitride nanotubes for extraction of angiotensin receptor blockers from human plasma.

The limitations of silica-based sorbents boosted the development of new extraction phases. In this study, boron nitride nanotubes functionalized with octadecyl groups were used for the first time as sorbent for extraction of losartan and valsartan, the most used angiotensin receptor blockers in the clinical practice, from human plasma. The nanotubes were synthesized using the chemical vapor deposition technique, purified by acid treatment, functionalized with octadecylamine in a microwave reactor, and characterized by different techniques.

Vortex-assisted liquid-liquid microextraction combined with liquid chromatography tandem mass spectrometry for simultaneous determination of cardiovascular drugs in human plasma.

Hypertension and dyslipidemias are among the main risk factors for the development of cardiovascular diseases, which are responsible for the death of approximately 17 million people each year. There are several drugs available for the treatment of these diseases. Therefore, methods for the simultaneous analysis of several of these drugs are useful in a wide range of situations.

Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes.

Liposomal amphotericin B (AmB) or AmBisome is the most effective and safe therapeutic agent for visceral leishmaniasis (VL), but its clinical efficacy is limited in cutaneous leishmaniasis (CL) and HIV/VL co-infection. The aim of this work was to develop a formulation of AmB in PEGylated liposomes and compare its efficacy to AmBisome in a murine model of CL. Formulations of AmB in conventional and PEGylated liposomes were characterized for particle size and morphology, drug encapsulation efficiency and aggregation state.

pH-sensitive doxorubicin-tocopherol succinate prodrug encapsulated in docosahexaenoic acid-based nanostructured lipid carriers: An effective strategy to improve pharmacokinetics and reduce toxic effects.

Side effects often limit the use of doxorubicin (DOX) in cancer treatment. We have recently developed a nanostructured lipid carrier (NLC) formulation for synergistic chemotherapy, encapsulating DOX and the anticancer adjuvants docosahexaenoic acid (DHA) and α-tocopherol succinate (TS). Hydrophobic ion-pairing with TS allowed a high DOX entrapment in the nanocarrier.

Multicomponent ionic crystals of diltiazem with dicarboxylic acids toward understanding the structural aspects driving the drug-release.

Diltiazem (DIL) is a calcium channel blocker antihypertensive drug commonly used in the treatment of cardiovascular disorders. Due to the high solubility and prompt dissolution of the commercial form hydrochloride (DIL-HCl) that is closely related to short elimination drug half-life, this API is known for exhibiting an unfitted pharmacokinetic profile. In an attempt to understand how engineered multicomponent ionic crystals of DIL with dicarboxylic acids can minimize these undesirable biopharmaceutical attributes, herein, we have focused on the development of less soluble and slower dissolving salt/cocrystal forms.

Chromatographic bioanalysis of antiglaucoma drugs in ocular tissues.

Glaucoma is a heterogeneous group of multifactorial optic neuropathies and the leading cause of irreversible blindness and visual impairment. Epidemiological data has estimated that in 2020 there will be more than 80 million individuals affected by the disease worldwide. Nowadays, intraocular pressure (IOP) lowering is carried out mainly by pharmacotherapy, with different drugs.

Simultaneous quantification of ethylene glycol and diethylene glycol in beer by gas chromatography coupled to mass spectrometry.

An analytical method for the simultaneous determination of ethylene glycol and diethylene glycol in beer was developed and validated according to current legislation. This method includes the application of sample dilution with ethanol followed by quantification using gas chromatography coupled to mass spectrometry. All figures of merit were within the limits established by regulation.

UHPLC for quality evaluation of genuine and illegal medicines containing sildenafil citrate and tadalafil.

One of the highest incidences of illegal drug products is related to phosphodiesterase-5 inhibitors, used in treatment of erectile dysfunction, including those containing sildenafil citrate and tadalafil. In this context, comprehensive evaluation of the quality of genuine and illegal medicines was performed. A simple and rapid ultra-high performance liquid chromatography (UHPLC-UV) method to quantify sildenafil and tadalafil in the presence of six degradation products was developed and validated.

Synthesis and characterization of a molecularly imprinted polymer (MIP) for solid-phase extraction of the antidiabetic gliclazide from human plasma.

Gliclazide is a sulfonylurea frequently prescribed for the management of type 2 diabetes mellitus in elderly patients and for patients with chronic renal or hepatic diseases. Even though it is considered a safer alternative, the drug can provoke side effects in some patients, especially hypoglycemia, due to the high interindividual variability. Therefore, the quantification of gliclazide in biological samples is usually recommended in order to assure efficacy and safety of the pharmacotherapy.

Microextraction by packed sorbent and high performance liquid chromatography for simultaneous determination of lumefantrine and desbutyl-lumefantrine in plasma samples.

A bioanalytical method for the determination of lumefantrine and its metabolite desbutyl-lumefantrine in plasma samples using microextraction by packed sorbent (MEPS) and high-performance liquid chromatography was developed and validated. A complete factorial planning and surface response approach were employed to optimize the extraction parameters sample volume, dilution, aspirated sample volume and extraction cycles. The method employed C18 MEPS sorbent and diazepam as internal standard (IS).

Enhancing the solubility and permeability of the diuretic drug furosemide via multicomponent crystal forms.

Furosemide (FSM) is a biopharmaceutical classification system (BCS) class IV drug, being a potent loop diuretic used in the treatment of congestive heart failure and edema. Due to its low solubility and permeability, FSM is known for exhibiting poor oral bioavailability. In order to overcome or even minimize these undesirable biopharmaceutical attributes, in this work we have focused on the development of more soluble and permeable multicomponent solid forms of FSM.

A simple and sensitive HPLC-FL method for simultaneous determination of angiotensin II receptor antagonists in human plasma.

Angiotensin II receptor antagonists are one of the most widely used classes of antihypertensive drugs. In this study, an HPLC fluorescence method after protein precipitation (PPT) extraction was developed and validated for determination of olmesartan, losartan, irbesartan, and valsartan in human plasma. The separation was carried out on a Luna cyano (250 × 4.

Novel self-nanoemulsifying drug-delivery system enhances antileukemic properties of all- retinoic acid.

All- retinoic acid (ATRA) shows erratic oral bioavailability when administered orally against leukemia, which can be solved through its incorporation in self-nanoemulsifying drug-delivery systems (SEDDS). The SEDDS developed contained a hydrophobic ion pair between benzathine (BZT) and ATRA and was enriched with tocotrienols by the input of a palm oil tocotrienol rich fraction (TRF) in its composition. SEDDS-TRF-ATRA-BZT allowed the formation of emulsions with nanometric size that retained ATRA within their core after dispersion.

Quantitative determination of the antimalarials artemether and lumefantrine in biological samples: A review.

Malaria is a worldwide health issue, with 216 million cases reported in 2016. Due to the widespread resistance of Plasmodium falciparum to conventional drugs, the first line treatment recommended by World Health Organization for uncomplicated malaria is artemisinin-based combined therapy (ACT), which combines two drugs with different mechanisms of action. The association of artemether and lumefantrine is the most common ACT used in the clinical practice.

A simple and rapid LC-MS/MS method for the determination of amphenicols in Nile tilapia.

A quantitative method for analysis of amphenicols (chloramphenicol - CAP, thiamphenicol - TAP and florfenicol - FF) in Nile tilapia using LC-MS/MS is described. A simple sample preparation procedure was optimized using a Plackett-Burman design. The method was validated in accordance with Decision 2002/657/EC.

Level A in vitro-in vivo correlation: Application to establish a dissolution test for artemether and lumefantrine tablets.

Malaria is the most incident parasite infection worldwide. Artemisinin based combination therapy (ACT) has been proposed as a promising treatment for malaria, and artemether + lumefantrine (20 + 120 mg) is the recommended association in endemic areas. Despite its widespread use, there is still scarce information about dissolution of artemether and lumefantrine, reflecting in the absence of a specific method in pharmacopoeias and international compendia.

Molecularly imprinted polymer for determination of lumefantrine in human plasma through chemometric-assisted solid-phase extraction and liquid chromatography.

Lumefantrine is the first-choice treatment of Falciparum uncomplicated malaria. Recent findings of resistance to lumefantrine has brought attention for the importance of therapeutic monitoring, since exposure to subtherapeutic doses of antimalarials after administration is a major cause of selection of resistant parasites. Therefore, this study focused on the development of innovative, selective, less expensive and stable molecularly imprinted polymers (MIPs) for solid-phase extraction (SPE) of lumefantrine from human plasma to be used in drug monitoring.