Drug Delivery Letters - Volume 9, Issue 4, 2019

Objective: Dendrimers, a new class of synthetic polymers proved themselves very useful tools for biomedical application due to their unique characteristics including water solubility, uniform size and shape, defined molecular weight, multivalency, biological compatibility and internal cavities. The hydrophobicity of a drug molecule creates hurdles in the development of effective dosage form and presents insufficient drug delivery to the target site Methods: Solubility enhancement is one of the key properties of a dendrimer. The hydrophobic drug molecules are entrapped in the cavities of a dendrimer by complexation and get solubilized in the aqueous solution. Conclusion: The present article contains information on dendrimer and its biomedical application such as API solubility. The detailed study presents year wise survey of different research articles, research papers, reviews and patents on dendrimer and its application in drug solubility.

Background: Conventional approach of formulating a new dosage form is a comprehensive task and uses various sources like man, money, time and experimental efforts. The use of AI can help to obtain optimized pharmaceutical formulation with desired (best) attributes. AI minimizes the use of resources and increases the understanding of impact, of independent variable over desired dependent responses/variables. Objective: Thus, the aim of present work is to explore the use of Artificial intelligence in designing pharmaceutical products as well as the manufacturing process to get the pharmaceutical product of desired attributes with ease. The review is presenting various aspects of Artificial intelligence like Quality by Design (QbD) & Design of Experiment (DoE) to confirm the quality profile of drug product, reduce interactions among the input variables for the optimization, modelization and various simulation tools used in pharmaceutical manufacturing (scale up and production). Conclusion: Hence, the use of QbD approach in Artificial intelligence is not only useful in understanding the products or process but also helps in building an excellent and economical pharmaceutical product.

Background: Peptide Hormones (PH) are mainly administered as parenteral injections due to their peculiar physicochemical properties, and susceptibility to enzymatic degradation after oral administration. With invasive routes, however, patient safety, acceptability, and compliance become a concern, especially when a patient has a chronic condition that requires repeated injections. The delivery of peptide hormones via the nasal route has gained momentum over the last few decades as a noninvasive alternative to parenteral injections and commercially available nasal liquid products. Objective: The aim of this paper was to review: (1) The benefits and limitations of nasal powder products, (2) Formulation strategies to enhance nasal delivery of peptide hormone drugs, (3) Nasal powder devices, and (4) Future perspectives of therapeutic nasal powders. The drugs examined specifically include calcitonin, desmopressin, ghrelin, glucagon, human growth hormone, insulin, octreotide, and oxytocin. Methods: Nasal delivery of peptide hormones using powders was reviewed with the following databases: EBSCO, PUBMED, Web of Science, ClinicalTrials.gov, and EU Clinical Trials Register. Results: Nasal powders are a promising drug delivery system that may be safer and more effective than traditional injections and presently marketed nasal liquids for peptide hormone drugs. Conclusion: With sustained interest and growing body of supporting evidence, a range of nasal powders for systemic delivery of these drugs and delivery devices can be expected to enter the market in the future and offer more options to patients.

Background and Objective: Ferrous ascorbate (FA) is preferentially absorbed from the upper gastrointestinal (GI) track, and has low bioavailability due to less residence time of FA in upper GI track. In addition, FA has low solubility and stability at higher pH. The aim of this study was to prepare gastro-retentive tablets of FA in order to increase its gastric residence time and hence, bioavailability. Methods: Floating tablets of FA were prepared by wet granulation method using different retarding polymers, Povidone K30 as binder and sodium bicarbonate as effervescent agent. The prepared floating tablets were compared with immediate release (IR) tablets and characterized in detail for in vitro and in vivo studies. Results: In-vitro drug release study of the optimized batch showed 96% drug release in 12 h in 0.1 N HCl. The mechanism of drug release from the floating tablets was non-fickian and release kinetics was best fit in peppas model. The gastric retention time of optimized was found to be significantly increased (6 h) in comparison with IR tablet (<1h). Further, bioavailability was also found significantly increased (>70%) in comparison with IR tablet (15-30%). X-ray studies carried on healthy rabbits suggested that the optimized batch remained buoyant in gastric contents up to 6 h and pharmacokinetic study showed sustained released behaviour of optimized batch in comparison to conventional IR tablet. Conclusion: Floating tablet of FA improved the bioavailability of iron by increasing its gastric residence time, hence it could be a better approach for treating iron deficiency and help in improving the patient compliance than IR tablets.

Background and Objective: Olanzapine (OLZ) is an atypical psychotic agent; the poor bioavailability of olanzapine is the most important issue in its treatment. The present work was carried out to evaluate the oral form of olanzapine solid lipid nanoparticles (OLZ-SLN) to overcome its poor bioavailability and compare between the effect of different doses of OLZ and OLZ-SLN on ketamineinduced schizophrenic-like symptoms. The study was extended to evaluate the adverse effects of subchronic administration of these doses of OLZ and its SLN. Methods: OLZ-SLN was prepared by hot homogenization, particle size, zeta potential and in vitro release and entrapping efficiency studies were performed. In order to assess the effective dose in the treatment of schizophrenia, the effect of different doses of OLZ and OLZ-SLN on open field was assessed and passive avoidance tests were carried out. The test was performed to examine the effects of excitatory and inhibitory amino acids, as well as dopamine and serotonin levels in the brain regions. Results and Conclusion: The new oral formula showed high stability and sustained release. The administration of low and high dose of OLZ-SLN equivalent to (1/10 and 1/20 from the therapeutic dose before ketamine attenuated the behavioral abnormalities by blocking the effect of ketamine-induced increase in glutamate, dopamine and serotonin levels and enhanced apoptosis were studied in the brain areas. In addition, the sub-chronic treatment with OLZ-SLN showed no adverse effect while the treatment with OLZ free form did.

Background: Onychomycosis is a nail fungal infection which accounts for 50% of the nail diseases and is characterized by disfigurement and discoloration of nails. The current therapy includes oral and topical formulations both of which come with their own drawbacks. This has left a room for developing patient- compliant novel strategies which can facilitate drug delivery deeper into the nails effectively. Objective: The main objective of the present work was to develop and evaluate in situ gelling thermosensitive hydrogel as an aqueous nail lacquer for the treatment of onychomycosis. The idea was to enhance permeation of Luliconazole into the nail while simultaneously solubilizing it in a hydrophilic formulation. Methods: The sample of Luliconazole was authenticated using modern analytical techniques. The hydrogel- nail lacquer was prepared using poloxamer Pluronic F127. The formulation was evaluated in terms of drying time, viscosity, non- volatile content, pH, transition temperature, etc. In vitro study was done to check the drug release while determining release kinetics. In vitro transungual permeation study was done to check drug permeation through porcine hoof membrane. Stability studies were conducted to ensure formulation stability. Results: The results confirmed a stable formulation with enhanced permeation through porcine hoof membrane. Conclusion: The results support the potential use of in situ gelling thermo-sensitive hydrogels as a novel transungual formulation in the treatment of onychomycosis with a slight improvement in water resistance.

Objective: The objective of the current research is systematic optimization and development of microemulsion preconcentrates to get better solubility that results in improvement of oral bioavailability profile of Telmisartan utilizing D-optimal mixture design. Methods: Solubility studies in a variety of lipidic ingredients and optimization of formulations were carried out for the development of liquid SMEDDS. D-optimal mixture design was utilized for assessing the interaction performance of desired responses (such as % cumulative drug release and globule size) and optimized using desirability approach. The optimized batch was evaluated for its % cumulative drug release and globule size performance for determining the dissolution rate and oral bioavailability of drug. Results: The optimized batch (F-8), which contained 10% oil (Capmul MCM EP), 45% surfactant (Labrasol) and 45% co-surfactant (Transcutol HP) resulted in desired qualities of measured responses with 84.6nm globule size and 98.5% drug release within 15 minutes. Optimized SMEDDS showed brilliant goodness of fit between drug release. Stability studies indicated stability of the optimized SMEDDS batch over 3-month storage at 40°C/75% RH and improved dissolution rate in contrast to pure API. The optimized SMEDDS showed no impact of in vitro lipolysis on drug release. Conclusion: Developed and optimized SMEDDS showed improved in vitro dissolution rate and dissolution profile in contrast to pure drug. These investigations further confirm dose reduction in SMEDDS by gaining an equivalent therapeutic profile with non-SMEDDS formulation. This research work successfully shows the potential usage of SMEDDS for delivery of BCS-II class drugs.

Background: Drug delivery across the buccal mucosal epithelium membrane is one of the promising routes to treat various recurrent ailments of the oral cavity. Aphthous stomatitis is an inflammatory oro-mucosal disorder associated with mucous membranes of mouth, cheek, lips, tongue or gingival region. Benzydamine Hydrochloride was designated as a drug of choice by virtue of its anesthetic, antimicrobial, analgesic, anti-inflammatory and antibacterial action. The medication administration through the buccal route is very testing because of restricted absorption area, shorter residence time and movements of the target region. Objective: To prepare mucoadhesive buccal gel of Benzydamine Hydrochloride and assess the effects of various HPMC polymer on in vitro and ex vivo performance with the assumption to extend the residence period and achieve maximum drug release in a sustained manner at the target region. Methods: Mucoadhesive buccal gels were formulated by utilizing various HPMC grades that served as rate controlling and mucoadhesive polymer. A total of 24 preparations were formulated and subjected to physicochemical evaluation and characterization. Results: It was found that the physicochemical parameters varied according to the polymer type and concentration used. Eight formulations were exposed to ex vivo study by virtue of maximum in vitro permeation and mucoadhesion properties. Because of higher ex vivo drug permeation and mucoadhesion, F24 was considered as the final optimized formulation. FTIR and DSC established compatibility between the drug and excipient. The amorphous nature of the drug within the optimized formulation was further unveiled by XRD study. Conclusion: The developed buccal gel has a great prospective in contrast to marketed conventional preparation for treating aphthous stomatitis.