Current Drug Delivery - Volume 10, Issue 2, 2013

Objectives: The aim of the present study was to formulate and characterize solid lipid nanoparticles (SLNs) of essential oil of Zataria multiflora. Methods: The essential oil was extracted from the leaves of Z. multiflora and was analyzed by GC-MS. SLNs were prepared using two methods including precipitation technique and hot homogenization method for achieving the best encapsulation. The SLNs were characterized by Differential Scanning Calorimetery (DSC), Transmission Electron Microscopy (TEM) and particle size analysis. The release of essential oil was determined using a dialysis membrane method. Key findings: The results showed that the encapsulation efficiency was 38.66%. Results of particle size determination showed a mean size of 650 nm and SLNs were spherical as shown by TEM. The DSC curve of sodium dodecyl sulfate (SDS), polyethyleneglycol (PEG), cetyl alcohol and essential oil were different from essential oil containing SLNs, which indicated that the essential oil can interact with the matrix of lipid during the preparation of the SLNs. 93.2% of the essential oil was released after 24 h. Conclusions: The results of characterization of the SLNs indicated the potential application of essential oil of Z. multiflora loaded SLN as carrier system.

Pharmacokinetic parameters of ketorolac tromethamine (KT) loaded albumin (KTAL) microspheres were determined using New Zealand white rabbits. Each rabbit (n=6) was injected 5 mg/kg body weight of plain KT or an equivalent dose in microsphere form in 2 mL water for injection. Prior to animal studies microspheres were tested for toxic residues and were gamma sterilized. Sterilized microspheres were evaluated for their integrity by physico-chemical characterization. Test for toxic residues was negative, the sterilization process utilized was effective and did not alter any physicochemical characteristics and showed good syringeability. When KT was administered in the form of microspheres there was a significant increase in Cmax, AUC, t1/2 and MRT (P < 0.05). When administered as microspheres, plasma concentration of drug sustained for 24 hours. It was concluded that KTAL microsphere formulation improved the systemic exposure and sustained the drug release and could be used for once-a-day administration of KT.

The aim of the present investigation was to prepare coumarin matrix transdermal systems using the combinations of Eudragit RL-100/Eudragit RS-100. The formulations were evaluated for various physicochemical properties (thickness, weight variation, drug content uniformity, moisture content and water absorption uptake), in vitro release studies, in vitro skin permeation studies and skin irritation studies. In vitro skin permeation and skin irritation studies were carried out on rat skin and rabbit respectively. The drug–polymer interaction results revealed no interaction between the drug and the polymers. Drug content uniformity of the patches was found more than 98%. Variations in drug permeation profiles were observed among the formulations. From the results concluded that coumarin can be formulated into the transdermal matrix type patches to overcome the first pass effect, reduced frequency of administration of coumarin and sustain its release characteristics; the polymeric composition Eudragit RL and Eudragit RS (1:1) with 1mL of ethanol was found to be the best choice for the formulation of transdermal patches of coumarin among the formulation studied.

The present studies entail the formulation development and evaluation of chronomodulated drug delivery system of amoxicillin trihydrate (AMT), which comprises of a bilayer tablet containing a delayed release and a sustained release layer. Direct compression method was employed for the preparation of bilayer matrix tablets containing rational blend of polymers, such as Eudragit-L100 D55 as delayed release polymer and HPMCK4M, HPMCK15 and HPMCK100 are sustained release polymers. In- vitro drug release studies of bilayer tablets observed a good sustained release action with time-dependent burst release after a lag-time of 3 hrs. Evaluation of drug release kinetics from sustained release layer of bilayer tablets followed Higuchi model via quasi-Fickian diffusion mechanism. SEM studies revealed formation of pores on sustained release layer, which confirmed the drug release through diffusion and predominantly by surface erosion mechanism. Evaluation of antimicrobial activity showed a decrease in minimum inhibitory concentration of optimized bilayer tablets vis-à-vis conventional marketed formulation. Accelerated stability studies revealed that the optimized bilayer tablet formulation was found to be stable upto the period of 6 months. Solid state characterization employing FT-IR and DSC studies indicated lack of significant interaction of drug with formulation excipients. Thus, the present studies ratify the suitability of chronomodulated bilayer tablets of AMT for effective management of bacterial infections owing to specific time-dependent drug release, higher gastric protection and enhanced antimicrobial activity.

Periodontitis is an inflammatory condition affecting teeth resulting in progressive destruction of periodontal ligaments, resorption of alveolar bone and loss of teeth. Treatment of periodontitis includes surgical and non surgical management. Systemic antibiotics are also used for the treatment of periodontitis. The aim of this research was to formulate smart gel system of azithromycin (AZT) and to evaluate in vitro and in vivo for non-surgical treatment of chronic periodontitis. Azithromycin dihydrate, used systemically in the treatment of periodontitis, was formulated into smart gels using biodegradable, thermosensitive polymer Pluronic® F-127 (PF-127) and Hydroxy Ethyl Cellulose (HEC) as copolymer. The prepared smart gels were evaluated for sterility, content uniformity, gelation temperature and time, syringeability, rheological behavior, in vitro diffusion and in vivo efficacy in human patients. The prepared smart gels were clear and transparent, sterile, thermoresponsive and injectable. Viscosity of gels increased with increase in concentration of polymer/co-polymer and also with temperature. They gelled in short response time below the body temperature. In vitro release studies showed controlled drug release which was influenced significantly by the properties and concentration of PF-127 and HEC. In vivo efficacy studies showed a significant improvement (p<0.001) in clinical parameters such as gingival index, probing pocket depth, clinical attachment level, bleeding index and plaque index. The developed azithromycin smart gel system is a novel approach for the treatment of chronic periodontitis since it reduces the dose and side effects, bypasses the usual surgical procedures and improves patient compliance.

Mucilages, and in particular plant mucilages, have gained more attention over the last few decades due to their reputable medicinal properties. Some publications have appeared in reputable Scientific Journals that have made appreciable contributions to the discovery of the functions and utilizations of such naturally occurring products. Therapeutic value of mucilages has been extended to wound healing, diabetes, immunostimulation, cancer, angiotensin converting enzyme inhibition, stomachic, and antioxidant properties. Based on their sustaining capacities as well as binding and gelling properties, mucilages have been proposed to be one of the most useful materials to modulate drug delivery. Chemical analysis reveals that generally these contain monosachrides along with a range of other organic and inorganic components. Although physiological properties of various plant mucialges have been described, it still remains uncertain as to which of the component(s) is responsible for these physiological properties. Further research needs to be done to unravel the myth surrounding the biological activities and the functional properties of them. This review presents an overview of the current status and knowledge on the applications of plant mucilages as therapeutic agent and pharmaceutical additives.

The development of the vectorized delivery systems combining advantages of the colloidal carriers, with active targeting to the receptors sites suggests that nanoparticles have a considerable potential for treatment after biophase internalization and pharmacokinetics, as for example gene therapy. Two major mechanisms can be distinguished for addressing the desired sites for drug release: (i) passive and (ii) active targeting. Examples of passive targeting were presented: organ targeting by the Enhanced Permeability and Retention (EPR) effect; targeting the mononuclear phagocitic system; organ targeting by chemoembolization or local (organ) administration;sterical stabilization of nanoparticles (PEGylation). A strategy that could allow active targeting involves the surface functionalization of drug carriers with ligands that are selectively recognized by receptors on the surface of the cells of interest. The source for biophase bioavailability can be the systemic bioavailability following common routes of adminstration (generally for systemic delivery of medicines), or directly the site specific biophase bioavailability for the formulations capable of cellular or nuclear drug internalization where the drug release only will take place (for nanoparticulate drug delivery systems, DDS). Once the pharmaceutical nanosystem was internalized, begins the release of the active moiety by different mechanisms, as for example the escape from endosome, or biodegradation of the polymer carrier or liberation of the active peptide or gene from a biological construct in the nucleus, etc. The presentation will discusses the pharmacokinetics of drugs after systemic administration but especially the biophase bioavailability and pharmacokinetics after the administration of biotechnology origin of therapeutic proteins like monoclonal antibodies, gene transfer products, plasmid DNAs, nucleotides, antisense oligonucleotides (AODNs) or small interfering RNAs (siRNA).

The present study deals with preparation, optimization and in-vitro drug release study of hydroxyapatite (HAp)- ofloxacin for bone-implantable delivery in osteomyelitis treatment. The effect of drug amount added, and orthophosphoric acid addition rate as process parameters on the drug loading into HAp-system by precipitation method was optimized by using 32 factorial design. The response surface methodology utilizing polynomial equation was used to search for optimal drug loading into HAp-system. The responses observed coincided well with the predicted values obtained through optimization technique. HAp-ofloxacin bone-implants were manufactured using synthesized HAp-ofloxacin composite powders and 2 % w/v aqueous solution of sodium alginate was used as binder. Characterization of the delivery system was done by FTIR spectroscopy. The in-vitro ofloxacin release from optimized HAp-ofloxacin bone-implants was slow and sustained over 10 weeks. The drug release pattern was correlated well with Korsmeyer-Peppas model and was followed by Fickian (diffusional) release mechanism.