Drug Delivery Letters - Volume 9, Issue 3, 2019

Background: Chitosan (CS) is a biomaterial derived from chitin, known for its excellent biological properties. One of the most interesting features of CS is its potential for chemical derivatization, which makes it a versatile material and allows to expand its applications. In the last years, the interest on this polymer and its pharmaceutical applications has notably increased. This biopolymer is being widely studied for its interesting properties, such as bioadhesion, antimicrobial activity, biocompatibility, and biodegradability. Other promising properties of CS include its modulation of immunological response, hemostasis, and wound and bone healing activity. Objective: In this work, a critical review is performed covering its conventional and novel applications, specially focused on pharmaceutical area, providing a clear picture of the current state of art to serve as a basis to direct future research in this field. Conclusion: Despite all the qualities of this polymer, there are only few CS-based products in the market, so it is a priority to enhance the research to develop new technologies and CS-based systems to enforce this biopolymer in the industry.

Background: Nasal drug delivery has been used since ancient times for therapeutic and recreational purposes. For the last decades, nasal drug delivery has been extended for drug delivery to the brain. Therefore, it is important to understand the several physiological and physicochemical factors of the nose for brain drug delivery. Objective: A major highlight of the present review article is the several aspects of the nose to brain delivery for migraine treatment. This review will help to understand different factors which are needed to be considered for intra-nasal formulations to achieve the desired therapeutic effects. Methods: There are different drug delivery routes available for migraine treatment. Nasal route of administration may be optimal for migraine treatment which has better drug concentration in the brain. These approaches may be associated with limiting the adverse effects of drug therapeutics. Results: A list of total FDA approved approaches has been provided. Novel approaches used for drug targeting to get maximum drug concentration in the brain have been highlighted. Several novel drug delivery approaches such as nanoparticle, nanoemulsion, microspheres, etc. have been reported and better therapeutic effects have been observed. Among the novel approaches, some of them are currently under either Phase II or Phase III development but may prove to offer better clinical effects. These approaches would become the alternate choice for migraine treatment with patients experiencing symptoms consistent with gastrointestinal dysfunction associated with migraine. Conclusion: Intra-nasal administration of drugs for migraine treatment may offer an interesting alternative for achieving therapeutic effects of drugs which are comparable to the parenteral route. Nasal drug delivery can be an alternative route of drug administration for migraine treatment to achieve better bioavailability.

Background & Objectives: Fungi are the heterotrophic eukaryotic organisms which are useful as they causes the biodegradation. There are still some harmful species like yeasts, molds and dermatophytes which cause the infections. As the fungi are eukaryotics, they do not respond to the antibiotic therapy due to the limitations associated with the traditional antibiotic therapies. There are several antifungal agents introduced to treat such infections. These antifungal agents posses severe problems like drug resistance and toxicity due to the higher dose which comprises the need for newer alternatives over conventional dosage forms. Novel drug delivery systems proved to be a better approach to enhance the effectiveness of the antifungals and enhance patient compliance by reducing the adverse effect. Discussion: This review focused on the general information about fungal infections, types and mechanism of action of antifungal agents and overview of formulation approaches such as vesicular system, colloidal system, nanoparticulate system and in situ gelling which are often studied for antifungal treatments. Conclusion: We concluded that the novel drug delivery systems are the essential techniques for delivering the antifungal agents to their target site with desired concentration. Moreover, the researchers focused on these novel drug deliveries which mainly concentrate on controlling & sustaining the release of antifungal agents.

Objective: The present research work is aimed at the development of an in situ gel polymer composite to provide local and sustained delivery of therapeutic agents in the vaginal cavity. Administration of medicated gel into a vaginal cavity is very complicated, inconvenient and needs expert assistance. There is a chance of expulsion of liquid formulation from site of application, leads to poor therapeutic efficacy. The effective drug delivery system for the vaginal cavity should be of liquid for application and gel to reside in the cavity. Methods: In situ gel composed of chitosan (0.8%) cross-linked with β-glycerol phosphate (15%) and glutaraldehyde treated guar gum (0.2%) was developed. Gel was characterized for in situ gelling properties. In vitro drug release pattern of the gel was tested on a nutrient agar medium containing attenuated E. coli and B. Subtilis. In vitro diffusion pattern of gel was tested using KC-diffusion cell with Simulated Vaginal Fluid (SVF) (pH 4.2) as the diffusion medium. Results: In situ gel exhibited sharpest sol-gel transition at 35±2°C, at pH 5.4 in 62±1.31sec. The viscosity of polymer composite is 51.25±3.68 CPs at 20±2°C and 328.56±4.16 CPs at 35±2°C. The gelation time of gel was found to be decreasing as the concentration of cross-linking agent β-GP increased. Formulations exhibited a shear thinning property. Drug release from this polymeric composite was found to be highly linear and follows non-fickian diffusion mechanism. Conclusion: This advanced thermosensitive in situ gel is convenient to apply and reside in the vaginal cavity for a prolonged period of time. The gel is mucoadhesive, biodegradable and suitable for controlled drug delivery in the cavity.

Background: Adapalene is a promising third generation retinoid used in the topical treatment of acne vulgaris. However, the major drawback associated with conventional topical therapy of Adapalene is the ‘retinoid reaction’ which is dose-dependent and characterized by erythema, scaling and burning sensation at the application sites. Microparticulate drug delivery can play a major role in reducing side effects and providing better patient compliance due to targeted delivery. Methods: Adapalene microparticles were prepared using quasi emulsion solvent diffusion method. The effects of formulation variables including polymer ratios, amounts of emulsifier, drug loading and process variables such as stirring time and speed on the physical characteristics of microparticles were investigated. The developed microparticles were characterized by DSC and SEM. Adapalene microparticles were incorporated into Carbopol 971 NF gel for ease of topical delivery. Results: Adapalene microparticulate topical gel showed sustained drug release over 8 hours in in vitro studies. The amount of drug retained in the rat skin during ex vivo studies was higher in the microparticulate topical gel (227.43 ± 0.83 μg/cm2) as compared to the marketed formulation (81.4 ± 1.11 μg/cm2) after 8 hours indicating localized and sustained drug action that can be useful in treating acne vulgaris. The safety of optimized Adapalene gel determined by skin irritation studies performed on Sprague Dawley rats showed no irritation potential. Conclusion: Microparticles can provide promising carrier systems to deliver Adapalene, improving patient compliance due to enhanced skin deposition, localized and sustained action with reduced associated irritant effects.

Background: The aim of the present study was to formulate and evaluate floating bioadhesive tablets of Nizatidine which is a competitive, reversible H2-receptor antagonist. Floatingbioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong gastric residence time was prepared. Methods: Polymers used were Hydroxy Propyl Methyl Cellulose (HPMC) K15M as matrix forming water swellable release retarding polymer and carbopol 934P as bioadhesive polymer. The gas generating agents used were sodium bicarbonate and citric acid. The prepared floating bioadhesive tablets of Nizatidine were optimized by 32 factorial design to study independent variable X1 (concentration of CP 934P) and X2 (concentration of HPMC K15M) and dependent variables as floating lag time, cumulative percentage drug release at 12h and swelling index. Tablets were evaluated for various parameters such as hardness, friability, drug content, swelling behavior, floating lag time, bioadhesive strength, drug release profile and stability. Results: All the formulations passed the test for weight variation, hardness, content uniformity and showed acceptable results with respect to drug content (97.93 ± 0.57) and % friability. The tablet containing 25% HPMC K15M and 13.75 % Carbopol 934P was selected as optimized formulation which showed the floating lag time of 74.34±2.08 seconds, drug release of 97.03±0.55% at 12 h (R12h,%), S.I as 79.24±0.87 at 9 h and bioadhesive strength as 10.0023±21.47 g. Stability of the formulation was proved using stability study. Conclusion: The formulated tablets have a potential for controlled release of the drug through floatation and bioadhesion.

Background and Objective: The top approach to deliver poorly soluble drugs is the use of a highly soluble form. The present study was conducted to enhance the solubility and dissolution of a poorly aqueous soluble drug nevirapine via a pharmaceutical cocrystal. Another objective of the study was to check the potential of the nevirapine cocrystal in the dosage form. Methods: A neat and liquid assisted grinding method was employed to prepare nevirapine cocrystals in a 1:1 and 1:2 stoichiometric ratio of drug:coformer by screening various coformers. The prepared cocrystals were preliminary investigated for melting point and saturation solubility. The selected cocrystal was further confirmed by Infrared Spectroscopy (IR), Differential Scanning Calorimetry (DSC), and Xray Powder Diffraction (XRPD). Further, the cocrystal was subjected to in vitro dissolution study and formulation development. Results: The cocrystal of Nevirapine (NVP) with Para-Amino Benzoic Acid (PABA) coformer prepared by neat grinding in 1:2 ratio exhibited greater solubility. The shifts in IR absorption bands, alterations in DSC thermogram, and distinct XRPD pattern showed the formation of the NVP-PABA cocrystal. Dissolution of NVP-PABA cocrystal enhanced by 38% in 0.1N HCl. Immediate release tablets of NVP-PABA cocrystal exhibited better drug release and less disintegration time. Conclusion: A remarkable increase in the solubility and dissolution of NVP was obtained through the cocrystal with PABA. The cocrystal also showed great potential in the dosage form which may provide future direction for other drugs.

Objective: The present study was aimed at developing and exploring the use of PEGylated Poly (propyleneimine) dendrimers for the delivery of an anti-diabetic drug, insulin. Methods: For this study, 4.0G PPI dendrimer was synthesized by successive Michael addition and exhaustive amidation reactions, using ethylenediamine as the core and acrylonitrile as the propagating agent. Two different activated PEG moieties were employed for PEGylation of PPI dendrimers. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release, hemolytic toxicity and blood glucose level studies of both PEGylated and non- PEGylated dendritic systems were determined and compared. Results: PEGylation of PPI dendrimers caused increased solubilization of insulin in the dendritic framework as well as in PEG layers, reduced drug release and hemolytic toxicity as well as increased therapeutic efficacy with reduced side effects of insulin. These systems were found to be suitable for sustained delivery of insulin by in vitro and blood glucose-level studies in albino rats, without producing any significant hematological disturbances. Conclusion: Thus, surface modification of PPI dendrimers with PEG molecules has been found to be a suitable approach to utilize it as a safe and effective nano-carrier for drug delivery.