Drug Delivery Letters - Volume 8, Issue 1, 2018

Background: Dendrimers are nano-sized drug delivery systems that present significant advantages, including ease of construction, large number of polymers available for their synthesis and amenability to affix various types of ligands for targeting to specific site. The nanosystem with unique functional architecture and macromolecular characteristics has garnered considerable interest amongst researchers and various research reports and patents inputs can be found in literature. Objective: Till date more than ten families of dendrimers have been reported for their wide applications in medicine including diagnostic/clinical, and also in industrial arenas. Unlike traditional polymers, many dendrimers have remarkable features like improved aqueous solubility, biocompatibility, polyvalency and precise molecular weight. These features make dendrimers an ideal vehicle for drug delivery and targeting applications. Conclusion: The current review is an attempt to define types of dendrimers and their applications in drug delivery and cosmetics. The write up also highlights future perspectives of the multifunctional nanosystem.w is an attempt to define types of dendrimers and their applications in drug delivery and cosmetics. The write up also highlights future perspectives of the multifunctional nanosystem.

Background: In spite of a tremendous development in the neuroscience, particularly in the area of drug delivery, only a few drugs have been marketed for central nervous system related disorders. Aim: The present work aims to comprehensively review the recent advancements in the nose to brain drug targeting and the challenges in its administration. Method: Most relevant and selected peer-reviewed articles based on nose to brain targeting were accessed from the various online scientific databases including PubMed, Scopus and Google Scholar. All these articles were thoroughly reviewed and their significant findings were described with further recommendation. Results: The nasal route for brain targeting can be considered as the most suitable one due to rapid drug absorption through the highly vascularised mucosa. Moreover, various properties such as easy administration, evasion of GIT and first-pass metabolism, non-invasive, better bioavailability, and fast action make this route highly acceptable. However, there are many factors which affect the brain targeting; these include drugs and formulation related factors. Hence, the particle size, shape, molecular weight, chemical form and solubility of the drugs as well as drug concentration, buffer capacity and viscosity of the formulation are equally important in the nose to brain targeting. Conclusion: The outcome of nasal route of drug targeting is not up to the mark due to rare studies on its efficacy, toxicity and clinical trials. Therefore, more advanced investigations are still required to make this unique method applicable for the betterment of mankind.

Background and Objectives: Inflammatory Bowel Disease (IBD) is a group of inflammatory conditions of the colon and small intestine. Crohn's disease and ulcerative colitis are the principal types of inflammatory bowel disease. IBD is a complex disease which arises as a result of the interaction of environmental and genetic factors leading to immunological responses and inflammation in the intestine. Curcumin, a yellow coloring agent is used as a remedy for the treatment and prevention of inflammatory disease. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. Methods: An attempt was made to formulate sustained release pellets of curcumin using Carboxymethyl Tamarind Seed Polysaccharide (CMTSP). Solid dispersion of curcumin prepared using soluplus and incorporated into pellets for enhanced solubility and bioavailability. A central composite design was applied to study the effect of independent variables (amount of microcrystalline cellulose MCC and CMTSP) on crushing strength and drug release of pellets. In vivo study of solid dispersion loaded pellets revealed the presence of more amount of drug in plasma than pure drug loaded pellets. Result: Dissolution and absorption of curcumin were found to be increased by 1.5 and 2 fold, respectively. Conclusion: Carboxymethyl tamarind seed polysaccharide can be used successfully for colon targeted drug delivery system in the form of pellets. The percent permeability of pellets prepared by using solid dispersion was found to be more than pellets prepared by using pure drug. Curcumin has an advantageous safety profile as well as low relativecost, making it an attractive option for IBD patients.

Background and Objective: The present work discusses the use of alkalizer based solid dispersion approach for solubility enhancement of Ibuprofen (IBP). Ibuprofen, a BCS Class II drug shows dissolution rate limited absorption and pH dependent solubility with higher solubility above pH 6.8. The poor aqueous solubility of IBP affects drug absorption and hence, therapeutic response as the drug is indicated in arthritis, pain conditions where rapid onset of drug action is essential to maintain functional ability. Methods: Solid dispersions of Ibuprofen were prepared by melt granulation technique using PEG 6000. The solubility of IBP in PEG 6000 was further improved by incorporating alkalizer which modified the micro environmental pH. Immediate release tablets of IBP were developed which showed pH independent drug release and significantly improved the rate of dissolution as evident from in vitro release and ex vivo permeation studies (Permeability co-efficient for pure drug and optimized tablet formulation were found to be 0.2044 and 0.6205 respectively). DSC and XRD studies indicated conversion of drug to an amorphous form which demonstrated solubility enhancement of IBP in the PEG melt with alkalizer. Conclusion: The developed formulation due to enhanced solubility and pH independent drug release can be absorbed in the gastrointestinal tract irrespective of the effects of physiological pH on drug solubility. Thus, the alkalizer based solid dispersion technique can prove beneficial in improving aqueous solubility and hence bioavailability of drugs.

Background: The oral route is the most preferred route of administration for selfmedication, but poor membrane permeability and pre-systemic degradation are key challenges that need to be addressed. Objective: The purpose of this study was to develop and evaluate a double-phase, multiple-unit dosage form for enhanced delivery of insulin across the gastrointestinal tract epithelium. The dosage form was designed to provide increased membrane permeation by opening of tight junctions during the first phase followed by insulin delivery during the second phase. Methods: Different beads were prepared by means of extrusion-spheronisation. Combinations of different beads constituted the double-phase drug delivery systems. The one type of bead contained insulin as active ingredient and chitosan as mucoadhesive agent, while the other bead formulations contained each one of the following drug absorption enhancers: a bile salt mixture, sodium glycocholate, Aloe vera whole leaf extract or Aloe vera gel. The insulin delivery performance of the different doublephase delivery systems was evaluated across excised pig intestinal tissues in a Sweetana-Grass diffusion apparatus. Results: Initial exposure of the excised pig intestinal tissues to the absorption enhancer containing beads (first phase) was associated with enhanced intestinal transport of insulin (second phase) when compared to the control group. The insulin permeation enhancement effect across excised pig intestinal tissue was statistically significant in the case of pre-exposure to A. vera whole leaf extract and A. vera gel containing beads. Conclusion: Several double-phase multiple-unit drug delivery systems have the potential to effectively deliver insulin across the gastrointestinal epithelium.

Background and Objectives: The aim of present research work was to develop and validate a discriminative dissolution method in order to quantify simvastatin (SIM) in various pharmaceutical preparations using High-Performance Liquid Chromatography (HPLC) and ultraviolet spectrophotometry (UV). Methods: The dissolution test was performed according to standard procedures by varying the concentration of Sodium Dodecyl Sulphate (SDS) in dissolution medium (pH 7.0 sodium phosphate buffer) in order to discriminate the impact of surfactant on dissolution rate enhancement of drug in various formulations. The aforementioned dissolution method was validated for linearity, specificity, accuracy, precision and robustness as per the ICH guidelines using HPLC and UV method. Results of dissolution test were analysed by HPLC and UV and statistically compared (P≤ 0.05) to select the best method for estimation of simvastatin in various formulations in developed medium. Results: 0.1 % SDS in dissolution medium was optimized as this concentration was able to display the actual effect of formulation on dissolution rate of drug. All results of validation parameters of developed dissolution medium were found to be satisfactory and in acceptable range for both analytical methods. Linearity was found to be 4 -60 μg/mL and 2 -16 μg/ml for HPLC and UV methods, respectively. The low value of RSD (<2%) in both cases indicates that both the methods are adequate. Statistically, no significant difference (P ≤ 0.05) was observed between the two. Conclusion: Discriminative dissolution method for the quantification of simvastatin was developed and validated successfully. The validated dissolution method may be employed for quality control and estimation of SIM in brand new formulations.

Objective: In the following study the cucumber starch was extracted from cucumber fruit as a natural source. Then it was used as a binder in tablet formulated by wet granulation methods. Further, it was evaluated by different parameters to study its effect on the solubility and dissolution rate of a drug. Methods: The fruit of cucumber has high content of starch and hence it can be used as a material for the extraction of starch. Then the extracted starch was evaluated and used as a binder in different concentrations, in famotidine tablets. The tablets were formulated by wet granulation method by using 2% w/v, 4% w/v, 6% w/v and 8% w/v of cucumber starch. Then the formulated famotidine tablets were further evaluated for various parameters i.e. weight variation, hardness, friability, disintegration time and invitro drug release. Results: The starch obtained was qualitatively and quantitatively compared to known standard starch. The hardness and disintegration time of the tablets was found to be increased with increase in starch concentration. Tablets with highest binder concentration showed maximum hardness (6.4 kg) and disintegration time (8.5 min) and minimum friability (0.38%). After one hour, the tablets with 2% w/v starch showed maximum drug release (81.84%). Conclusion: The results from various evaluations show that cucumber starch has significant binding characteristics. Hence, it can be used as a tablet binder in pharmaceutical formulations.

Objective: The objective of the present work was to develop curcumin transdermal films by solvent evaporation technique using Carboxy polymethylene and Eudragit RS 100 as matrix polymers. The influence of penetration enhancers: dimethyl sulphoxide (1, 2 and 3% (w/w)), tween 80 (1, 2 and 3% (w/w)) and oleic acid (1, 2 and 3% (w/w)) on the in vitro percutaneous absorption of Curcumin through the rabbit skin was evaluated. Methods: Differential scanning calorimetry was used to evaluate the compatibility between the drug and excipients. All the prepared formulations were evaluated for moisture content, moisture uptake, flatness, tensile strength, drug content determination and in vitro permeation studies across rabbit skin. Results: The enhancing effectiveness of the enhancers decreased in the order: Oleic acid > Dimethyl sulphoxide > Tween 80. Compared to the control formulation 1.3-fold enhancement was observed with 2% tween 80. There were no significant promoting effects at low concentrations of dimethyl sulphoxide; however, a 1.18-fold increase in Curcumin flux resulted in higher percentage (3%) of dimethyl sulphoxide. The highest enhancement factor was 1.43 with 2% oleic acid. The skin irritation tests showed negligible erythema and edema. Conclusion: The results suggested the possibility of using formulated curcumin films in topical conditions like wound healing.