Drug Delivery Letters - Volume 4, Issue 3, 2014

This recent research work was aimed to develop the oral dissolving films of gliclazide. Solid dispersions of gliclazide using natural polymers such as hupu gum (HG), guar gum (GG) and xanthan gum (XG) were prepared by kneading technique and the optimized solid dispersion was exploited to develop the gliclazide films. Different grades of HPMC (E5, 50 cps and K4M) were used to develop the films by adapting solvent casting method. Six formulations (FG1-FG6) of gliclazide films were prepared. The films were evaluated for their thickness, tensile strength, elongation, weight variation, folding endurance, drug content uniformity and surface pH and obtained satisfactory results. The films were assessed for their compatibility between the drug and excipients by FTIR and DSC techniques. The film formulations were subjected to disintegration, in vitro drug release and pharmacodynamic studies. From the results FG4 formulation was found as best formulation which contains HPMC K4M and gliclazide solid dispersion with guar gum at weight ratio of 1:2. The formulation had showed excellent film characteristics such as disintegration time of 64 sec and drug release was 97.30 % within 10 min. The optimized film formulation (FG4) showed excellent stability over 45 days when stored at 40°C /60% RH. The pharmacodynamic study in animal models (rats) proved that fast dissolving films of gliclazide produced a faster onset of action compared to that of conventional formulation.

Cystic fibrosis (CF), a genetic lethal chronic disease, causes the body to produce abnormally thick and sticky mucus. As a consequence following bacterial infections threaten ten thousands of people around the world every year. Available tests enable early diagnosis of CF. Nevertheless, current treatments can only serve to improve patient’s quality of life. Despite the fact that life span of CF patients is dramatically increased with comprehensive treatments during the last decades, there is no ultimate prevention or cure for CF. Chronic respiratory infections are known to be the major cause of morbidity and mortality. Since the airways provide direct access to these bacteria, it is an attractive target for drug delivery against bacterial infections in CF lung. Current pulmonary treatments are, however, limited since reaching the site of action is highly inhibited by the biofilm, which establishes an efficient obstacle for drug diffusion. Recent developments in nanotechnology have led many researchers to study different types of nanoparticles and nanoformulations for pulmonary drug delivery in the scope of providing a solution to current treatment bottlenecks. This review focuses on the development of nanoparticulate antibiotic pulmonary drug delivery systems for the treatment of Pseudomonas aeruginosa infected CF lungs.

Amphotericin B (Amb) is a broad-spectrum polyene macrolide antibiotic which has been a drug of choice for fatal conditions like fungal splenic abscess. Hence a drug delivery system with splenotropic potencial might be of great significance for further therapeutic effectiveness. Present manuscript proposes development of Irregular shaped polymer lipid hybrid nanostructures (LIPOMER) of Amb with enhanced splenic uptake. Amb LIPOMER (~400 nm) was prepared using poly(methylvinylether-co-maleic anhydride) [Gantrez® AN119] and glyceryl monosterarate (GMS) as matrix material. Conditions for preparation of formulation were optimized using 23 factorial design and effect of the concentration of excipients on the particle size and entrapment efficiency was evaluated. Optimized formulation was further characterized using Transmission electron microscopy (TEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier transformed infrared spectroscopy (FTIR) techniques. Amb LIPOMER exhibited acceptable haemolysis when assessed for In-vitro hemolytic potential in comparison to Fungisome TM. The high splenic uptake of Amb LIPOMER was verified using gamma scintigraphic technique in small animal model. Results of our study indicated that LIPOMER system can be a smart drug delivery platform for Amb to eradicate splenic infections effectively.

The objective of the present study was to formulate bilayer matrix tablets containing aceclofenac as sustained release and paracetamol as immediate release using HPMC as the matrix forming polymer and the tablets were evaluated via in-vitro studies. In-vitro drug release studies were carried out in hydrochloric acid buffer of pH 1.2 (0.1N) with 1% w/v SLS using USP paddle apparatus. The amount of drugs released at different time intervals were determined by validated UPLC-PDA method. In-vitro drug release from prepared tablets showed better effect when compared with marketed combination tablets. Tablets thus formulated provided sustained release of aceclofenac over a period of 12 h and paracetamol as immediate release within 30 min.

In the present work, an attempt was made to develop and evaluate composite microspheres for controlled release of an anti-diabetic drug, nateglinide (NTG). The composite microspheres were prepared using rosin gum and ethyl cellulose as retardant polymers for drug release by solvent evaporation method. DSC and XRD analysis indicated the uniform dispersion of drug in the microspheres. The microspheres were capable of releasing drug for 24 h and the drug release mechanism followed non-Fickian transport. In vivo anti-diabetic activity conducted on wistar rats indicated that the plain (unformulated) NTG showed maximum percent reduction in blood glucose up to 2 h and then the blood glucose was increased. While in case of rats treated with test microspheres (RN6), the percent reduction in glucose level was slow up to 2 h as compared to plain drug, then it was gradually increased to 72.83 % at the end of 24 h. Histopathology of rat pancreas suggested that the regeneration of β cells was seen in the rats treated with RN6 microspheres. It can be concluded from the study that, the prepared microspheres are versatile delivery systems for nateglinide, which could release drug for longer period of time.

The effect of stainless steel microneedle arrays and rollers on transcutaneous flux of captopril and metoprolol tartrate across full thickness porcine skin was studied. Captopril is an angiotensin converting enzyme (ACE) inhibitor used for the management of hypertension. It has a partition coefficient (log P) of 0.35 and a molecular weight of 216.7 g/mol. Metoprolol tartrate is a β-adrenergic blocker also used for the management of hypertension. It has a log P of 1.6 and a molecular weight of 267.3 g/mol. The properties of these anti-hypertensive agents limit the amount of the drugs that can cross the skin. To overcome this limitation, stainless steel microneedles were used to enhance transdermal delivery of these therapeutic agents. Two types of microneedle designs were used in the study- a microneedle roller and a microneedle array. In vitro diffusion studies were carried out using vertical Franz diffusion studies (PermeGear, Hellertown, PA, USA). The receptor chamber contained 12mL of phosphate buffer saline (PBS) and the donor chamber contained 1mL of captopril or metoprolol tartrate solution. The diffusion area was 1.77cm2 and full thickness porcine skin was clamped between the two chambers. There were six untreated porcine skin samples. In the study, there were 2 Franz cells with a donor phase consisting of the same solvent as used to make the drug solutions, but without the drugs. Experiments were carried out in six replicates. Six samples served as controls. Aliquots of 1ml were withdrawn every 2 hours and analyzed with liquid chromatography. The results showed that transdermal flux values for captopril and metoprolol tartrate increased from 75.04 µg/cm2/hr to 608.2 µg/cm2/hr and 62.28 µg/cm2/hr to 290.93 µg/cm2/h respectively following the use of microneedle arrays. Transcutaneous flux for captopril increased from 19.68µg/cm2/hr to 1485.20 µg/cm2/hr, whereas metoprolol tartrate flux increased from 84.64 µg/cm2/hr to 226.08 µg/cm2/hr after treatment of pig skin with microneedle rollers. Our results demonstrate that there was statistically significant enhancement in transdermal flux (p <0.05) of captopril and metoprolol tartrate after application of microneedle arrays and rollers. Together, these results demonstrate that stainless steel microneedle arrays and rollers can increase permeation of captopril and metoprolol tartrate across the skin. It may be possible to use this appealing alternative to create a simple and effective needle based system to deliver therapeutics across the skin.

Nowadays natural or herbal products are more often used in comparison to synthetic products because of their low toxicity, biodegradability, biocompatibility and cheaper cost. An effort has been made to design and characterize buccal films of glimepiride using natural polymer. The natural polymer was extracted from Trigonella foenumgraecum L(Methi) seed. The polymer was extracted by solvent extraction method and was characterized for different parameters i.e., physical characteristics, bulk density, tapped density, Carr’s index, swelling index, pH and angle of repose. Solubility behavior of the isolated mucilage, with different solvents, was also studied. It was found that mucilage was insoluble in cold water but soluble in hot water. The buccal films were formulated using solvent casting technique. The main polymer used was Methi polymer. Different concentrations of polymer were used in the development of buccal film. The formulated films were evaluated for different parameters i.e., surface pH, weight uniformity, tensile strength, disintegration, swelling index, in vitro drug release, drug content, thickness and folding endurance. pH of the formulated films was between 6.8 and 7.4. The drug content of films was in the range of 7.3-9.3. In vitro drug release study showed an average 85% drug release from all the formulated films upto 6 hrs. Swelling index of the formulated films showed good swelling upto 2 hrs. It was showed that Formulation F3 was the best formulation among all the formulations. In the optimized batch, the polymer concentration was 300 mg/25 ml.

Dissolution of drug from solid dosage form is explained by kinetic models i.e. zero order, first order, higuchi model, Hixson-crowell cube root law, Korsmeyer-peppas and weibull model. These models are effective as design of new delivery device and the existing device is optimized by these models. In this study, these models are classified on two different bases. All these models are explained including their kinetic equations, plot which describes the relationship between drug release and time, and their applications. These models are best explained by examples including polymer and drug which show release behaviour following different models.