Developing and advancing dry powder inhalation towards enhanced therapeutics.

Enhanced therapeutics are drug products derived from existing generic drugs that provide additional benefits to the patients and the healthcare system. Enhanced therapeutics are considered to be an important and relatively low risk source of innovation. Pulmonary drug delivery is the major delivery route to treat chronic respiratory diseases and has been proven as a potential delivery route for complex drugs that cannot be delivered orally.

Long-circulating PEG-PE micelles co-loaded with paclitaxel and elacridar (GG918) overcome multidrug resistance.

Overexpression of drug efflux pump P-gp is one of the major reasons to cause multidrug resistance (MDR). To overcome P-gp mediated MDR, modulators, so called P-gp inhibitors, can be used to block efflux pump activity. Elacridar is one of the most potent P-gp inhibitors, which can cause irreversible and total P-gp blockage.

PEG-PE-based micelles co-loaded with paclitaxel and cyclosporine A or loaded with paclitaxel and targeted by anticancer antibody overcome drug resistance in cancer cells.

The over-expression of the P-glycoprotein (P-gp) in cancer cells is one of the main reasons of the acquired Multidrug Resistance (MDR). Combined treatment of MDR cancer cells with P-gp inhibitors and chemotherapeutic agents could result in reversal of resistance in P-gp-expressing cells. In this study, paclitaxel (PTX) was co-encapsulated in actively targeted (anticancer mAb 2C5-modified) polymeric lipid-core PEG-PE-based micelles with Cyclosporine A (CycA), which is one of the most effective first generation P-gp inhibitors.

Development and validation of an HPLC method for simultaneous determination of trimethoprim and sulfamethoxazole in human plasma.

The combination of trimethoprim (TMP) and sulfamethoxazole (SMX) is used in the treatment of many common infections such as urinary, respiratory and gastrointestinal tract infections. The aim of this study was to determine TMP and SMX simultaneously in human plasma samples by high performance liquid chromatography (HPLC) using antipyrine as the internal standard. Separation of the compounds was achieved on a reverse-phase C8 column packed with 5 microm dimethyl octadecylsilyl bonded amorphous silica (4.

Optimization of prednisolone acetate-loaded chitosan microspheres using a 2(3) factorial design for preventing restenosis.

Prednisolone acetate (PA)-loaded microspheres were prepared by the spray-drying technique using different polymer (1% and 2%) and drug concentrations (10% and 20%). To obtain the optimum formulation, a three-factor two-level (2(3)) design was employed. The independent variables were polymer molecular weight, polymer concentration, and theoretical drug loading.

Development and characterization of liposomal formulations for rapamycin delivery and investigation of their antiproliferative effect on MCF7 cells.

Rapamycin (Sirolimus) is a macrolide lactone with antifungal, immunosuppressant, and antiproliferative actions. The mechanism of rapamycin action involves the inhibition of mTOR and subsequent cytostasis. Rapamycin also prevents angiogenesis in tumors and can prevent cancer cells' resistance to other chemotherapeutic agents.

Recent advances and future directions in amphiphilic cyclodextrin nanoparticles.

Cyclodextrins are known to be promising excipients in the pharmaceutical industry, with their ability to include hydrophobic guest molecules masking the physicochemical properties of the guest, such as poor water solubility, stability problems and undesired side effects. These enabling excipients, which are produced on a large scale and incorporated into various marketed products worldwide, are now modified to render amphiphilic properties that enable them to be used to prepare nanoparticles. Amphiphilic cyclodextrins have the ability to form nanoparticles without the presence of a surfactant by different preparation techniques that are discussed in this review.

Development of biodegradable drug releasing polymeric cardiovascular stents and in vitro evaluation.

Prednisolone acetate (PA) is insoluble in water and was chosen as a model drug for its anti-inflammatory/anti-proliferative functions. PA is incorporated into the film-based polymeric biodegradable stents to provide controlled local release of the drug during the mechanical support phase. Stent formulations were 3 mm in diameter with lengths of 150 mm.

Hyaluronic acid coated poly-epsilon-caprolactone nanospheres deliver high concentrations of cyclosporine A into the cornea.

The objective of this study was to determine cyclosporine A (Cy A) levels in ocular tissues and fluids after topical administration of poly-epsilon-caprolactone (PCL)/benzalkonium chloride (BKC) nanospheres and hyaluronic acid (HA) coated PCL/BKC nanospheres onto healthy rabbit corneas. Nanospheres were prepared by nanoprecipitation and purified by gradient-rate centrifugation. Cy A (0.

Hepatic disposition of trimethoprim and sulfamethoxazole.

Hepatic disposition of trimethoprim (TMP) and sulfamethoxazole (SMX) and the liver distributional volumes were investigated in the in situ perfused rat liver preparation. Perfusion experiments were conducted using Krebs-bicarbonate buffer delivered via the portal vein (15 ml/min) in a single-pass mode. Erythrocytes (intravascular marker) and Evans blue (extracellular marker) were used for the estimation of liver distributional volumes, and desiccation and freeze-drying methods were used for the estimation of liver water content.

Pharmacokinetics and bioequivalence study of a generic amlodipine tablet formulation in healthy male volunteers.

Two different tablets containing amlodipine besylate (CAS 111470-99-6) (Vazkor 10 mg tablet as test preparation and 10 mg tablet of the originator product as reference preparation) were investigated in 18 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence between both treatments after oral single dose administration. The study was performed according to an open-label, randomized, two-period cross-over design with a wash-out phase of 21 days. Blood samples for pharmacokinetic profiling were taken up to 144 h post-dose, and amlodipine plasma concentrations were determined with a validated LC-MS/MS method.

Development of nonsurfactant cyclodextrin nanoparticles loaded with anticancer drug paclitaxel.

In the current formulation of clinical use paclitaxel (PCX) is associated with solubilizers that may produce severe side effects. In this study, PCX was complexed to an amphiphilic cyclodextrin (CD), 6-O-CAPRO-beta-CD, capable of forming nanoparticles spontaneously in order to mask its physicochemical properties via the formation of inclusion complexes of the drug with amphiphilic CD before the nanoparticle is formed. Complexes have been characterized with various techniques such as (1)H NMR, Fourier Transform Infrared (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) confirming the formation of inclusion complex between PCX and 6-O-CAPRO-beta-CD.

Safety and efficacy of amphiphilic beta-cyclodextrin nanoparticles for paclitaxel delivery.

Paclitaxel is a potent anticancer agent with limited bioavailability due to side-effects associated with solubilizer used in its commercial formulation and the tendency of the drug to precipitate in aqueous media. In this study, paclitaxel was encapsulated in amphiphilic cyclodextrin nanoparticles. Safety of blank nanoparticles was compared against commercial vehicle cremophor:ethanol (50:50 v/v) by hemolysis and cytotoxicity experiments.

Pharmacokinetics and bioequivalence study of doxycycline capsules in healthy male subjects.

The aim of the present study was to compare the bioavailability of doxycycline (CAS 564-25-0) from two different doxycycline hyclate (CAS 24390-14-5) capsules (Monodoks 100 mg capsule as test preparation and 100 mg capsule of the originator product as reference preparation) in 24 healthy male subjects. The study was conducted according to an open-label, randomised two-period cross-over design with a wash-out phase of 16 days. Blood samples for pharmacokinetic profiling were taken up to 72 h post-dose, and doxycycline plasma concentrations were determined with a validated HPLC method with UV-detection.

Pharmacokinetics and bioequivalence study of ranitidine film tablets in healthy male subjects.

The aim of the present study was to compare the bioavailability of ranitidine (CAS 66357-35-5) from two different ranitidine hydrochloride (CAS 66357-59-3) film tablets (Ranitab 150 mg film tablets as test preparation and 150 mg film tablets of the originator product as reference preparation). The study was conducted according to an open-label, randomised two-period cross-over design with a wash-out phase of 9 days. Blood samples for pharmacokinetic profiling were taken up to 24 h post-dose, and ranitidine plasma concentrations were determined with a validated HPLC method with UV-detection.

Pharmacokinetic and bioequivalence study of meloxicam tablets in healthy male subjects.

Meloxicam (CAS 71125-38-7), a non-steroidal anti-inflammatory drug (NSAID), is used for the treatment of osteoarthritis and rheumatic arthritis. In the present study, two different oral meloxicam formulations (Melcam 15 mg tablets as test preparation and tablets of a reference preparation) were investigated in 24 healthy male subjects in order to prove bioequivalence between both preparations. A single 15 mg oral dose was administered according to an open, randomised, two-period cross-over design in the fasted state.

Bioequivalence study of sultamicillin suspensions.

Sultamicillin (CAS 76497-13-7) is a prodrug combination of ampicillin (CAS 69-53-4) and sulbactam (CAS 68373-14-8), with the antibiotic ampicillin and the beta-lactamase inhibitor sulbactam chemically linked as double ester. The present study was performed to investigate the relative bioavailability and to assess the bioequivalence of two different sultamicillin suspensions (Devasid 250 mg/5 ml as test preparation and 375 mg/7.5 ml of the originator product as reference preparation).

Comparative pharmacokinetics of two tablet formulations of amoxicillin: bioequivalence assessment.

The aim of the present study was to compare the bioavailability of amoxicillin (CAS 26787-78-0) from two different amoxicillin tablets (Demoksil 1 g tablet as test preparation and 1 g tablet of the originator product as reference preparation). The study was conducted according to an open-label, randomised two-period cross-over design with a wash-out phase of 4-7 days. Blood samples for pharmacokinetic profiling were taken up to 10 h post-dose, and amoxicillin plasma concentrations were determined with a validated LC-MS/ MS method.

Formulation and characterization of formaldehyde cross-linked degradable starch microspheres containing terbutaline sulfate.

Preparation of starch microspheres using epichlorohydrin is a time consuming method and requires around 18 hr for cross-linking reaction. To reduce reaction time, terbutaline sulfate (TBS) loaded degradable starch microspheres (DSM) were prepared using formaldehyde as the cross-linking agent. All microspheres were spherical in shape and had a porous, rough surface with a mean particle size of 18-24 microm.

Implantation of vancomycin microspheres in blend with human/rabbit bone grafts to infected bone defects.

In orthopaedic applications, allografts are used for restoration of bone defects. In order to combine the effects of bone repair and to prevent the infection, antibiotic-impregnated bone grafts are under current investigation with promising early results. In this study, to preserve the stability of antibiotics and to provide appropriate release profiles for 4-6 weeks, antibiotic-loaded microspheres were administered in combination with allografts and vancomycin was the antibiotic loaded to microspheres.

Effect of drug physicochemical properties on in vitro characteristics of amphiphilic cyclodextrin nanospheres and nanocapsules.

Nanospheres and nanocapsules of an amphiphilic beta-cyclodextrin, beta-CDC6, were evaluated using a group of steroid drugs to determine the effect of drug physicochemical properties (e.g. partition coefficient, drug:CD association constant k1:1, aqueous solubility) on loading and release profiles of the nanoparticles.

Potential use of freeze-drying technique for estimation of tissue water content.

Desiccation and freeze-drying methods were used for the estimation of water content of various rat tissues. In the desiccation method, the tissue samples were cut into small pieces and subsequently dried at 40 degrees C to constant weight. In the freeze-drying method, the prefrozen tissue samples were freeze-dried (-50 degrees C) for 24 h.

DEET-loaded solid lipid particles for skin delivery: in vitro release and skin permeation characteristics in different vehicles.

DEET (N,N-diethyl m-toluamide) is a lipophilic compound which has a common use as an insect repellent and causes not only skin irritation but also systemic side effects at high concentrations in long-term skin application. In this study, DEET is incorporated into solid lipid particles, a colloidal drug delivery system, in order to reduce the percutaneous permeation and avoid toxic effects and also maintain drug effectiveness on the skin surface for a long duration of insect repellence. Solid lipid particles were prepared based on emulsion systems at different concentrations and after the characterization studies, the formulation with 20% lipid phase and 1:1 drug:lipid ratio was carried to in vitro release and skin permeation studies.