Drug Delivery Letters - Volume 10, Issue 4, 2020

Formulation development of BCS Class II and IV drugs is a challenging task due to their poor solubility and permeability issue. An extensive literature survey was conducted to explore the relevant pharmaceutical approaches that have been used for solving the issue of poor solubility and permeability in the recent past. It has been found that a plethora of approaches have been investigated for addressing the issue of poor solubility and or permeability. These include physical modifications (modification of crystal habit, particle size reduction, complexation, polymorphism and drug dispersion in carriers), chemical modifications (salt formation), and formulation modifications (Nanotechnology-based approaches and hydrotropy). The physical and chemical modification approaches can be effectively used to enhance the solubility and dissolution rate of poorly soluble drugs, but the additional problem of poor permeability has been better addressed by lipid-based drug delivery systems. As the latter presents the drug in the solubilized state, bypass first-pass effects, circumvent the effect of Para-glycoprotein mediated efflux of drugs, hence contributing to overall bioavailability enhancement.

Statins are the choice of drugs for the treatment and management of hypercholesterolaemia because of their established lipid-lowering efficacy and safety profile. Among the various statins, simvastatin is a very popular antihyperlipidemic drug with pleiotropic effects that have a wide range of applications such as antioxidant, anti-inflammatory, antifibrotic effect as well as angiogenic activity. However, poor biopharmaceutical characteristics like low solubility and high permeability make this drug more challenging for formulation scientists in terms its delivery to different targeted areas. Oral drug delivery systems, lipid nanoparticles, PLGA nanoparticles, sustained-release tablets, matrix-type transdermal, co-encapsulating nanostructured lipid carriers are some of the strategies that have been explored to address this issue. This review provides an update regarding the disease, destination, dose and delivery associated with this wonderful lipid-lowering drug molecule.

Nose to brain drug delivery system is an interesting approach to deliver a drug directly in the brain through the nose. Intranasal drug delivery is very beneficial because it avoids first-pass metabolism and achieves a greater concentration of drugs in the central nervous system (CNS) at a low dose. This delivery system is used for the treatment of various neurological disorders such as Parkinson's disease, Alzheimer's disease, schizophrenia, dementia, brain cancer, etc. To treat such types of diseases, different formulations like nanoparticles (NPs), microemulsions, in situ gel, etc. can be used depending on the physiochemical properties of the drug. In this review, some essential characteristics related to the delivery of nose to the brain and their possible obstacles are underlined, which include anatomy and physiology of nose to brain delivery. This review also summarizes innovations from the past three to five years.

Aims: The purpose of this study was to investigate and compare the formation of polymeric and Ocimum gratissimum seed films containing solid lipid particles for controlled drug release. Methods: The hot homogeneous method was selected to form solid lipid particles containing sodium fusidate to load the drug into the film. The in vitro drug release and drug permeability of the films were tested with dialysis tubes and the Franz diffusion cell method, respectively. The mucoadhesive time and swelling and erosion rates were also studied. Results: The solid lipid particles showed the ability to form Ocimum gratissimum seed and polymeric films for use in drug delivery. Although the polymeric matrix yielded excellent swelling and erosion rates, leading to a faster drug release rate and drug permeation than that of the Ocimum gratissimum seed film, the mucoadhesive time of the polymer film was worse than that of the seed film. Conclusion: Therefore, the characteristics of the individual systems may be further studied in a combined system to take full advantage of both in the desired film.

Background: Formulating protein drugs into delivery systems with high drug loading is particularly challenging. Another major hurdle for formulation processes generally used for protein drugs is their scalability. In this article, we present the application of spray drying to prepare polymeric microparticles of human recombinant IL-1 receptor antagonist (IL-1 ra). Objective: The objective of this study was to formulate polymeric microparticles entrapping a therapeutic protein, human recombinant IL-1 ra using a spray drying process. Methods: IL-1 ra was formulated using three polymers viz. gelatin, pectin, and sodium alginate by using a spray drying process to produce polymer entrapped drug microparticles. A single drug to polymer ratio was used in the three drug-polymer formulation combinations. The prepared microparticles were evaluated for morphology by scanning electron microscopy, average particle size by dynamic light scattering and drug entrapment efficiency by ELISA. Results: Microparticles of three drug-polymer combinations were prepared using the Buchi B-90 spray dryer. The morphology of the three types of polymeric microparticles was found to be uniform by scanning electron microscopy. The average particle size for the three formulations ranged from 1 to 2.2 μ with a low standard deviation implying narrow particle size distribution. The drug loading efficiency ranged from 62 to 90 % W/W for the three formulations. Conclusion: The presented study demonstrates the feasibility of using spray drying to prepare morphologically uniform polymer entrapped protein drug microparticles with high drug entrapment efficiency.

Objective: The present investigation was aimed to isolate, characterize and establish a natural polymer obtained from partially ripe and fresh fruits of Dillenia indica and its utility to deliver losartan potassium in a sustained manner from microspheric macromolecular dosage form. Methods: All the microspheres were prepared by ionotropic gelation technique and investigated for various physico-chemical parameters along with in-vitro drug release studies to optimize the concentration of algino-Dillenia polymeric blend required to develop twice daily sustained release dosage form of losartan potassium. Results: The functional characteristic studies and rheological behavior analysis suggested that extracted polysaccharide can be used as a viscosity modifying agent as well as sustain release ingredient. All the microsphere formulations exhibited excellent mucoadhesion properties and site-specific drug release. In-vitro studies revealed that the optimum concentration of algino-Dillenia polymeric blend is suitable to deliver losartan potassium in a sustained manner for a prolonged period of time. SEM study revealed that the microspheres were spherical in shape with a smooth outer surface having small cracks. XRD and DSC studies revealed that losartan potassium is present as an amorphous form in the prepared optimized microsphere formulation. Conclusion: Thus, the present studies demonstrated that Dillenia fruit mucilage has an interesting rheological behavior which may be used as a viscosity modifying agent and exhibit promising properties of a sustained release dosage form to deliver losartan potassium from its microspheric dosage form.

Aims: The present study aimed to evaluate the healing effect of five new dermal ointments made with natural ingredients, derived from the Ficus microcarpa fruit, Pulicaria odora L. leaf powder, vaseline, lanolin, and sweet almond oil on thermal burns of New Zealand rabbits. Background: Many natural ingredients are used as alternatives in topical burn wound treatments. However, the effectiveness of an ointment is primarily assessed on the basis of the healing time. The latter depends on the synergetic effect resulting from the interaction of its different constituents. Hence there is the need to explore different formulations to find the most optimal one. Objectives: 1/ To evaluate some biochemical compositions, biological properties, and functional quality of F. microcarpa fruit and P. odora L. leaf powder., 2/ To identify the best combination between the F. microcarpa fruit, P. odora L. leaf powder, vaseline, lanolin, and sweet almond oil to obtain an ointment with high healing quality. Methods: Ten (10) New Zealand rabbits (5 males and 5 females) received two thermal burns caused by a hot cylindrical metal on their backs. Each rabbit was treated immediately thereafter with one of the elaborated ointments and with a commercial skin ointment Madecassol (reference). All the ointments were applied topically every other day until a complete epithelialization takes place. Evaluation of the healing process was based on the healing time and diameter narrowing calculated every seven days. Results: The obtained results show that all the developed ointments used in the experiments lead to total recovery with fur growth. However, the healing time varies from one formula to another. Conclusion: The study concludes that the combination of the natural active ingredients used in this study promotes burn wound healing in the rabbit’s model.