Drug Delivery Letters - Volume 2, Issue 3, 2012

Reformulation of anti-tuberculosis drugs into dry powder particles for inhalation is a novel strategy that aims to increase therapeutically relevant drug concentration at the primary site of infection and to limit associated toxicity by avoiding or minimizing first-pass metabolism. Development of such formulations ultimately requires quantified evidence of the deposition, absorption and clearance of inhaled active ingredient. In this context, we investigated the potential of radiolabelling particles with 153Sm for subsequent gamma imaging, and to demonstrate that the technique is not detrimental to particle integrity. The study showed that the known properties of spray dried leucine (a major constituent of an inhalable capreomycin formulation) for deep lung inhalation are not altered by incorporation of samarium-chloride (SmCl3) at 10% (w/w), or by neutron activation of particles that include stable 152SmCl3. SEM imaging indicated that the particle morphology was homogeneous and spherical after neutron activation. No discoloration of the samples or a change in dry powder particle size at 5 minutes occurred, provided the optimized formulations were activated for only 1 minute. Activation for 1 minute still provides enough 153Sm for imaging purposes.

The present study investigates the specific drug targeting of anti cancer drugs, such as carboplatin by incorporation into folate conjugated Solid Lipid Nanoparticles (SLN). Our results showed that SLN 5 has the greater entrapment efficiency of 87.50% and slow in-vitro drug release (65.31% of carboplatin was released in 12 hrs) among all the SLN formulations prepared by high speed homogenization using 23 factorial design. Then SLN 5 was further conjugated with folic acid and its mean particle size (312.208 nm) and in-vitro drug release in 12 hrs (63.43 %) were determined. The comparative in-vitro cytotoxicity for market formulation (Kemocarb), SLN and folate conjugated SLN was determined by MTT assay in Hep 2 cell line and the results showed that folate conjugated SLN has greater cytotoxicity of 70.64 % as it can specifically target the cancer cells through the folate receptors. In-vivo studies were carried out in female Wistar rats and the pharmacokinetic parameters were determined for the market formulation and folate conjugated SLN. The increase in the MRT and AUC values reflects the sustained release effect of folate conjugated SLN formulation and it confirms that it acts as a slow release carrier of carboplatin.

To reduce the risk of infection in the treatment of long bone defects, implant materials can be provided with an antibiotic drug delivery system. A novel bone implant for the tissue engineering of critical long bone defects was developed by stacking embroidered scaffolds, seeded with mesenchymal human stem cells. Controlled drug release is to be integrated in this implant by coating the thread material with antibiotics incorporated in a resorbable polymer matrix. A predictable release with defined and steady-going dosages must be guaranteed. Scaffolds, embroidered from a degradable surgical poly(caprolactone-co-lactide)-thread, were provided with an antibiotic depot by dip-coating them in a poly(lactide-co-glycolide) (RESOMER RG 756) solution with the antibiotic gentamicin sulfate distributed as suspended grains. Influence on the releasing profile is taken by varying grain size and grain size distribution. Antibiotic load in a required range could be achieved and an influence of the grain size on the releasing profile could be verified. The required initial and daily dosages could be realized and were exceeded in most of the cases. As optimum an approximated zeroorder kinetic in a time interval from 1 to 24 hours could be attained.

This systematic review and meta-analysis is focusing on the evidences related to iontophoresis used to enhance the topical drug delivery through the skin in the treatment of inflammatory dysfunctions, acute soft tissue injuries and pain. A literature search in the databases, MEDLINE (PubMed), Pedro, and the Cochrane Database of Systematic Reviews was conducted. The methodological quality of the obtained studies was independently rated by two reviewers. Data were pooled from those studies in which the effect of iontophoresis treatment on pain was compared with a control or sham (placebo) intervention. Twenty four experimental studies evaluating the effectiveness of iontophoretic treatment were included. Based on comparable statistical outcome for pain, the results of ten studies could be pooled for metaanalysis. Although several clinical studies claimed an advanced healing process after iontophoresis, controversy on the healing efficacy of iontophoresis remains. The overall summary estimate of the pooled post treatment values for pain was -0.672 [95%CI: -0.970 to -0.375] favouring iontophoresis treatment (p < 0.0001). The observed trend between studies heterogeneity for the post treatment pain values was low to moderate (I2 = 39.9%; p = 0.092). The results of the metaanalysis indicate quantitative evidence that iontophoresis is effective in the treatment of pain, however, the lack of solid research design in studies on iontophoresis makes it difficult to ensure that the improvements observed can be explained by the iontophoresis technique in se.

The aim of the presented work describes the formulation of compressed orally disintegrating tablet (ODT) using α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a binder/disintegrant. Preliminary investigations were focused on process and formulation optimisation which resulted in ODT containing 2% wt. TPGS with reasonable hardness and acceptable disintegration time but with high friability. The next stage of the work was to systematically investigate various strategies to overcome high friability including hot-cold cycle of powder blending to promote interparticular adhesion, size separation of diluent, influence of compression force and incorporation of crospovidone. The study concluded that friability was controlled by multi-strategic approach which resulted in reduction from 3.16% to 1%.

High blood pressure (HBP) is a serious condition that can lead to coronary heart disease, stroke, kidney failure and other health problems. Management of HBP with the conventional dosage forms of the existing antihypertensive agents are challenging to the clinicians. Candesartan cilexetil (CC) is a newer class of antihypertensive agent which comes under angiotensin II receptor antagonist. The current commercial formulation of CC is an immediate release and is administered twice daily. However, CC exhibited low oral bioavailability (only 15%) due to its poor aqueous solubility. Therefore, in the present study our aim was to formulate controlled release floating tablets of CC to minimize the untoward effects, patient compliance and improve the drug bioavailability. Fusion technique was used to formulate the drug and excipients into solid lipid microparticles (SLMs), which were then formulated as floating tablets using ethylcellulose as a polymer, and sodium bicarbonate and citric acid were used as gas generating agent. The microparticles and floating tablets were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy and x-ray diffractometry. The obtained solid lipid microparticles were spherical in shape with particle diameter ranging from 38 to 48 µm. No new peak was observed in the x-ray diffractogram, suggesting the absence of interaction between drug and excipients. Compared to other formulations (F1-F8), F5 showed maximum in vitro drug release of 96.19% for 24h. Thus, our results confirm that floating tablets of CC is a novel method of development to improve the bioavailability of the drug and hence the floating tablets of CC would be a new potential drug delivery for the treatment of HBP.

The purpose of this work was to formulate a controlled release multiple emulsion of carbamazepine favorable for administration in pediatrics and geriatrics suffering from epilepsy, decreasing the dosing frequency, thereby improving patient compliance and providing a platform for personalized medicine. Two–step emulsification procedure was employed for the formulation using liquid paraffin oil, water, surfactants and hydroxypropyl methylcellulose as the stabilizer. 2(4) full factorial design was applied for the optimization of the formulations consistent with the quality by design approach. The response variables were 1st hour release, 5th hour release, and time for 90% drug release and % entrapment efficiency. The optimized batch formulated with 8% w/w Span 60, 3% w/w Tween 80, 0.5% w/v hydroxypropyl methylcellulose (in internal aqueous phase) and the phase volume ratio of 1:1:2 was found to exhibit entrapment efficiency of >70% and zero order release profile. The similarity factor of 71 was obtained on release profile comparison of the 200mg/10ml optimized batch and the marketed Tegretal XR® 200 mg tablets. Carbamazepine being an autoinducer has high half life during the initiation of therapy which decreases during the course of maintenance therapy which requires the dose to be increased. The release profile of 100mg/5ml emulsion and 200mg/10ml emulsion both sufficed the criteria for >30% drug release in 1st hour and prolonged drug release up to 10 and 12 hours respectively. Hence through this research, personalization of therapy was claimed, to titrate the dosing needs according to the individual requirements during the initiation and maintenance therapy.

The goal of our study was to prepare carboplatin niosomes for enhanced delivery to cancer cells by thin film hydration technique using (cholesterol: surfactant) in the micromolar ratio of 30:100 and with/without the addition of charge inducing agents and Pluronic F 68. Photomicrographs of the formulations show the presence of multilamellar vesicles in the forumulation with Tween 80 and Pluronic F 68. The vesicle size of the formulation was found to be in the size range of 0.01-1µm. Carboplatin niosome formulation without any charge inducing agent and Pluronic F68 shows good drug entrapment (89.24%) with an in vitro release of 87.23% in 12 hours. Drug release kinetics of the formulation follows the Non Fickian diffusion mechanism and exhibits first order release kinetics. The in vitro cytotoxicity results of the formulations reveal that the Tween 80 formulation with Pluronic shows the highest level of cytotoxicity (90%) when compared with drug in solution. Also, the stability studies of the formulations reveal that the formulations were stable in refrigerated condition.