Atilla A. Hincal

• PhD Pharmaceutical Technology Biopharmacy
• Professor Emeritus at Hacettepe University (Former)

Aims: The aim of this study was to evaluate the pharmacokinetic profiles and the relative bioavailability of dexketoprofen and thiocolchicoside of the test preparation (dexketoprofen / thiocolchicoside 25 mg / 8 mg effervescent tablet) in comparison with the reference preparations (Keral 25 mg film coated tablet, containing dexketoprofen trometamol...

Cyclodextrins are cyclic oligosaccharides obtained by enzymatic digestion of starch. The α-, β- and γ- cyclodextrins contain respectively 6, 7 and 8 glucopyranose units, with primary and secondary hydroxyl groups located on the narrow and wider rims of a truncated cone shape structure. Such structure is that of a hydrophobic inner cavity with a hyd...

As a result of the long term collaboration and friendship between Prof. Dominique Duchene and Prof. Atilla Hıncal, several co-supervised Ph.D. theses were conducted in the frame of a co-tutelle PhD programme within the period of 2000–2007, based on the joint Ph.D. agreement between the Hacettepe University in Ankara, Turkey, and the Universite Pari...

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 ha...

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. Elacridar, among with oth...

Introduction: Our aim was to develop an anticancer drug- and p-gp inhibitor-co-loaded long-circulating polymeric micelles for the reversal of multidrug resistance (MDR). For this aim, PEG-PE-based micelles co-loaded with Paclitaxel (PTX) and P-gp inhibitors Cyclosporine A (CYA) or Elacridar (ELC) and further modified with nucleosome-specific mAb 2C...

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 active...

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 int...

Today we know that some active substances used in the treatment or those contained in the formulation of some dosage forms are not optimally and specifically delivered to target areas. In particular, toxicity and adverse effects of active substances used in cancer treatment, their effect on not only the target organ that needs treatment but also on...

Terbutaline sulphate (TBS) is widely used in the treatment of bronchial asthma, chronic bronchitis and emphysema. Because of its short biological half life and dosing schedule, a long acting TBS formulation is required to improve patient compliance. The objective of this study was to develop a TBS containing biodegradable microsphere formulation. P...

The objective of this study was to improve poor aqueous solubility and dissolution properties of anticancer drug rapamycin through formation of inclusion complexes with natural and modified cyclodextrins. Of the cyclodextrins tested, γ-cyclodextrin and hydroxypropyl-γ-cyclodextrin did not complex with rapamycin. However, complexes of rapamycin with...

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 d...

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. However, very poor wate...

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 incorporate...

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. However, very poor wate...

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...

The purpose of this study was to investigate by in vitro methods whether an interaction takes place between propranolol hydro-chloride and adsorbents when antacids are taken concomitantly with the beta-blocker or when excipients having adsorbent properties are present in formulations of the drug products containing propranolol hydrochloride. Specif...

Abstract Microspheres offer the possibility of target selectivity through choice of appropriate size or surface charecteristics, slow release of drug and also minimize systemic toxicity. The active substance of this investigation, cyclophosphamide (CP), interferes with the growth of cancer cells which are eventually destroyed. Since side effects of...

Abstract Caffeine has recently been found to cure atopic dermatitis, presumably by increasing skin levels of cAMP.In the light of these findings, its release from different ointment bases at varying concentrations was investigated in vitro. The ointment bases used were a petrolatum (named as petrolatum A), a PEG ointment (USP XVIII), a hydrophilic...

Two nonionic surfactants (Simulsol 98 and Simulsol OL 50) alone and I:I mixtures, corn oil-undecylenic acid and water formed emulsions, oily isotropic liquid phases, lamellar and hexagonal liquid crystal phases. The optimum release of undecylenic acid from these phases were controlled microbiologically. The active ingredient undecylenic acid, is re...

Abstract Recurrent Aphthous Stomatitis (RAS) is the most common form of nontraumatic oral mucosal ulceration. Numerous studies have suggested a wide variety of the probable etiologic mechanisms (1). However, various therapeutic approaches that have been made to date are controversial since the etiopathology has not been evidently elucidated yet. Co...

One of the principal uses suggested for the microencapsulation of pharmaceuticals has been the preparation of the sustained release dosage form. The finished microcapsules have usually been presented in the form of suspensions or gels, but in order to obtain greater sustained release effect a non-disintegrating tablet would be a better formulation....

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...

The dissolution test is intended to measure the time required for a given drug in an oral solid dosage form to go into solution under specified set of conditions. It is used to assess the batch-to-batch quality of a drug product, guide to development of a new formulation, ensure continuing product quality, support the bioavailability of a new produ...

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 compl...

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...

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...

This study describes the preparation and characterization of a model protein (bovine serum albumin; BSA)-loaded alginate microspheres. BSA was encapsulated within alginate microspheres by the emulsification technique. The average particle size was 11.96±0.043 μm of the prepared microspheres. The drug loading and encapsulation efficiency were about...

Cyclodextrins (CDs) have a wide range of application in the pharmaceutical field due to their unique structure, which allows them to include hydrophobic molecules in their apolar cavity and to mask the physicochemical properties of the included molecule. CDs have also been incorporated into nanoparticulate drug delivery systems for complexation of...

Inclusion complexes of the poorly-soluble antiestrogen drug tamoxifen citrate (TMX) were prepared with β-cyclodextrin (β-CD) and 2,3-di-O-hexanoyl-β-cyclodextrin (β-CDC6) being natural and amphiphilic cyclodextrins, respectively using the co-lyophilization technique. Complexation occurred in aqueous medium for natural cyclodextrin β-CD and a medium...

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 porou...

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 admi...

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, ra...

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-l...

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 p...

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-o...

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-lac-tamase inhibitor sulbactam chemically linked as double ester. The present study was performed to investigate the relative bioavailability and to assess the bioequivalence of two differen...

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 pro...

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. Tissue w...

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 percut...

Nanoparticles were prepared using beta-CDC6, which is an amphiphilic beta-cyclodextrin derivative modified on the secondary face with 6C aliphatic esters. A nanoprecipitation technique was used to prepare the blank nanoparticles without any surfactant and nanoparticles containing Pluronic F68 as surfactant in a concentration range of 0.1 to 1%. Nan...

Chitosan and poly(lactide-co-glycolide) acid (PLGA) microspheres loaded with alendronate sodium (AS) were prepared for orthopedic as well as dental applications. In orthopedics the aim was to make the total joint prostheses stay in the body for a long time without causing bone tissue loss, while in dentistry it was aimed to treat the alveolar bone...

Sterility is required as stated by compendial requirements and registration authorities worldwide for an injectable drug carrier system. In this study, injectable nanospheres and nanocapsules prepared from amphiphilic beta-cyclodextrin, beta-CDC6, were assessed for their in vitro properties such as particle size distribution, zeta potential, nanopa...

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. Model drugs used were hydrocor...

The purpose of this study was to achieve a better therapeutic efficacy and patient compliance in the treatment for vaginitis. Clotrimazole (1%) has been formulated in a vaginal gel using the thermosensitive polymer Pluronic F127 (20%) together with mucoadhesive polymers such as Carbopol 934 and hydroxypropylmethylcellulose (0.2% for both). To incre...

Poly (lactic-co-glycolic acid) (PLGA) microspheres containing all-trans retinoic acid (atRA) were prepared by emulsion/solvent evaporation technique. PLGA (50:50) with inherent viscosities of 0.17 and 0.39 dL g(-1) was used. Polyvinyl alcohol (PVA) or PVA and sodium oleate (SO) combinations (4:1) were used to stabilize the emulsions. The effect of...

This article describes the preparation and characterization of BSA and bFGF-loaded PLGA microspheres and assesses the effect of entrapment procedure and in vitro release conditions. In the experiments, changing the PVA concentration from 3 to 5% (w/v) in the pre-emulsion inner phase led to a change in particle size and encapsulation efficiency of B...

This study describes the preparation and evaluation of mitoxantrone (MTZ)-loaded chitosan, bovine serum albumin (BSA) and poly(D,L-lactide-co-glycolide) (PLGA) microsphere formulations in vitro and investigation of the in vitro bioactivity of the released drug (for BSA microspheres) or that obtained by extraction from microspheres (microencapsulate...

The inhibition of the caspase-3 enzyme is reported to increase neuronal cell survival following cerebral ischemia. The peptide Z-DEVD-FMK is a specific caspase inhibitor, which significantly reduces vulnerability to the neuronal cell death. However, this molecule is unable to cross the blood-brain barrier (BBB) and to diffuse into the brain tissue....

Treatment of central nervous system (CNS) diseases with potentially useful pharmaceuticals is prevented by the blood-brain barrier (BBB). The BBB is a unique protective barrier in the body. It is formed by epithelial-like tight junctions, which are expressed by the brain capillary endothelial cells. Although most molecules are potentially active in...

The natural polymers sodium alginate (SA) and chitosan were used for the preparation of SA and chitosan treated sodium alginate (CTSA) beads. Alendronate sodium (AS), which is a potent inhibitor of osteoclast-mediated bone resorption and used for the treatment of bone disorders, was loaded into the SA and CTSA beads prepared for implantation in ost...

Nanospheres and nanocapsules of beta-CDC6, amphiphilic beta-cyclodextrin modified on the secondary face with 6C aliphatic esters, were prepared with nanoprecipitation technique directly from inclusion complexes of tamoxifen citrate and beta-CDC6 (1:1 molar ratio). Blank and loaded nanospheres and nanocapsules were characterized by particle size dis...

The irritation effects of ibuprofen, a widely used non-steroidal anti-inflammatory drug (NSAID), were evaluated on mouse gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. The ionotropic gelation method was used to prepare controlled release alginate beads of ibuprofe...

Multilamellar liposomes containing 5-fluorouracil (5-FU) were prepared by modified lipid film hydration method and were lyophilized with or without saccharose as cryoprotectant. The effect of lyophilization on the stability of liposomes was evaluated by comparing the vesicle size, encapsulation efficiency and the drug release rate before and after...

The purpose of this study was to prepare and characterize injectable carbidopa (CD)/levodopa (LD)-loaded Poly(L-lactides) (L-PLA), Poly(D,L-lactides) (D,L-PLA) and Poly(D,L-lactide-co-glycolide) (PLAGA) microspheres for the intracerebral treatment of Parkinson's disease. The microspheres were prepared by solvent evaporation method. The polymers' (L...

The objective of the present study was to investigate the effect of polymorphism on in vitro-in vivo properties of carbamazepine (CBZ). For this purpose, three different polymorphs and a dihydrate of CBZ were obtained and the conventional tablets of these crystalline forms at the dose of 200 mg were prepared. The polymorphs were examined by the IR...

In the present study, the preparation and characterization of bovine serum albumin (BSA) microspheres and the evaluation of the in vitro cytotoxicity of these microspheres on acute promyelocytic leukaemia (HL-60) cells were described. Mitoxantrone (MTZ)-incorporated microspheres were evaluated for particle size, drug loading, release characteristic...

Retinoic acid microspheres were formulated using PLGA (50:50) polymer with solvent evaporation technique. In-vitro characterization of microparticles were determined. Retinoic acid microspheres were prepared by a yield of 42,79%. The average particle size was measured to be 3,291µm. Total drug content in microspheres were determined to be 1,65% and...

The HPLC method used for determination of mitoxantrone was validated by linearity, sensitivity, precision, accuracy and specificity. Retention time for mitoxantrone was 4.3 min and that for haloperidol (internal standard) 7.9 min. Calibration curves were constructed for mitoxantrone over the concentration range 0.25-5 μg.mL-1 (haloperidol, 2 μg.mL-...

Liposome gels bearing an antineoplastic agent, 5-fluorouracil, intended for topical application have been prepared and drug release properties in vitro have been evaluated. Different formulations of liposomes were prepared by the film hydration method by varying the lipid phase composition (PL 90H/cholesterol mass ratio) and hydration conditions of...

Chronic osteomyelitis is still the cause of many problems in orthopaedics in terms of therapy and infection persistence. Four-to-six week systemic antibiotic therapy is required along with bone and soft tissue debridement in the therapy of chronic osteomyelitis. Prolonged-release local antibiotic therapy has been taken into consideration due to the...

The influence of hydroxypropyl beta-cyclodextrin (HPbetaCD) on the corneal permeation of pilocarpine nitrate was investigated by an in vitro permeability study using isolated rabbit cornea. Pupillary-response pattern to pilocarpine nitrate with and without HPbetaCD was examined in rabbit eye. Corneal permeation of pilocarpine nitrate was found to b...

Amphiphilic beta-cyclodextrins were formulated as nanospheres and characterised by particle size, zeta potential and TEM following freeze-fracture. The nanospheres were loaded with progesterone with different loading techniques involving the spontaneous formation of nanospheres from pre-formed inclusion complexes of amphiphilic beta-cyclodextrins m...

The aim of this work was to develop and characterize a highly loaded nanoparticulate system based on amphiphilic beta-cyclodextrins (CDs) to facilitate the parenteral administration of poorly soluble antifungal model drugs bifonazole and clotrimazole. Inclusion complexes were characterized with spectroscopic techniques. Particle size distribution o...

dosage forms, attempts are being made to utilize drug carriers that ensure adequate localization or penetration of the drug within or through the skin in order to enhance the local and minimize the systemic effects, or to ensure ad-equate percutaneous absorption (1). The application of liposomes as drug carriers on the skin surface has been proven...

End-stage liver disease accounts for over 30,000 deaths annually in the United States. Orthotopic liver transplantation is the only clinically proven treatment for patients with end-stage liver failure. A limitation of this therapy is a shortage of donor ...

Terbutaline sulfate is widely used as a bronchodilator for the treatment of bronchial asthma, chronic bronchitis and emphysema. As it has a short biological half-life, a long acting terbutaline sulfate formulation is desirable to improve patient compliance. Bovine serum albumin microspheres were prepared by an emulsion polymerization method using g...

Alginate beads containing 5-fluorouracil (5-FU) were prepared by the gelation of alginate with calcium cations. Alginate beads loaded with 5-FU were prepared at 1.0 and 2.0% (w/v) polymers. The effect of polymer concentration and the drug loading (1.0, 5.0 and 10%) on the release profile of 5-FU was investigated. As the drug load increased, larger...

Parenteral antibiotic therapy for acute bone infections, soft tissue infections and osteomyelitis may result in high serum concentrations, associated with nephrotoxic, ototoxic and allergic complications. After taking these above mentioned disadvantages into consideration, recent investigations have explored the use of antibiotic-loaded biodegradab...