Improved Dissolution of Albendazole from High Drug Loaded Ternary Solid Dispersion: Formulation and Characterization

Bioavailability of a poorly water-soluble drug, e.g., widely used anthelmintic drug Albendazole (ABZ), is very low and thus, to obtain an optimized therapeutic efficacy, the aqueous solubility of such drugs needs to be enhanced. The objective of this study was to develop an effective high drug-loaded solid dispersion (SD) of ABZ with two biocompatible drug carriers, namely Soluplus® and Ludiflash® to improve its physicochemical characteristics. Equilibrium solubility study was performed to choose the optimum polymer ratio among the formulations and it showed up to 50-fold enhanced solubility compared to crystalline ABZ in water. X-Ray Powder Diffraction (XRPD) and Differential Scanning Calorimetry (DSC) studies of SD-ABZ showed reduced crystallinity of ABZ in the SD. The polymeric carriers, notably Soluplus®, are thought to play a key role in the reduction of crystallinity and molecular polydispersity of ABZ. The dissolution studies in water showed improved dissolution of SD-ABZ compared to crystalline ABZ, with a quick onset of drug release followed by gradual dissolution. However, due to high drug-loading and retention of crystalline ABZ in the sample, the dissolution behavior was not as expected, and may require further studies to optimize the SD-ABZ formulation. Dhaka Univ. J. Pharm. Sci. 20(2): 149-158, 2021 (December)

In vivo and in silico Evaluation of Analgesic and Hypoglycemic Activities of Roots of Acacia nilotica, Azadirachta indica and Justica adhatoda

The present study focuses on the investigation of methanol extracts of roots of three indigenous plants of Bangladesh namely Acacia nilotica, Azadirachta indica and Justicia adhatoda to evaluate their analgesic and hypoglycemic activities in experimental animal model along with in silico modelling of several compounds present in the root extracts of these plants. Analgesic and hypoglycemic activities were evaluated in Swiss albino mice using acetic acid-induced writhing inhibition method and glucose tolerance test, respectively. In silico molecular docking and ADME study was conducted to assess the binding affinity with the target receptors and oral bioavailability of the compounds. The methanol extracts of A. nilotica, J. adhatoda and A. indica roots at a dose of 400 mg/kg body weight reduced the number of writhes by 61.53%, 54.61% and 47.69%, respectively compared to standard diclofenac sodium (70.77% at a dose of 50 mg/kg bw) (p<0.05). A. nilotica and A. indica root extracts showed significant hypoglycemic activity at a dose of 400 mg/kg bw (% reduction of blood glucose 43.66 and 37.55% respectively, p<0.001) and J. adhatoda root extract reduced the blood glucose level by 33.71% (p<0.001) compared to that of standard drug, glibenclamide (57.46% reduction of blood glucose) after 120 minutes of administration. Among the computationally tested compounds, flavan-3-ol showed the lowest binding energy (-8.7 kcal/mol) with both COX-1 and COX-2 compared to standard diclofenac sodium (-7.8 kcal/mol). On the other hand, quercetin demonstrated the lowest binding energy (-8.8 kcal/mol) with ATP-sensitive potassium channel with Sulfonylurea Receptor 1 subunit among the tested compounds compared to standard glibenclamide (-9.3 kcal/mol). All the compounds showed high oral bioavailability in ADME analysis. Among all the root extracts, A. nilotica exhibited the most promising analgesic and hypoglycemic activities and should be employed to future investigation for isolating specific chemical constituents. Dhaka Univ. J. Pharm. Sci. 20(2): 185-197, 2021 (December)

Nanoemulgel: a Promising Nanolipoidal-Emulsion Based Drug Delivery System in Managing Psoriasis

Nanomedicine, a novel concept, bears much hope in delivering drug candidates having low solubility and bioavailability. Nano-emulgel, one of the emerging tools, is considered as ideal carriers for the topical delivery of lipophilic drugs to overcome these challenges in the management of psoriasis and related skin problems. Psoriasis is an auto-immune and chronic inflammatory disease affecting 2-3% population of the world. Current available treatment of psoriasis has limitations such as systemic side effects and low percutaneous permeation, which evokes a dire need to develop an alternative lipoidal nanocarrier system. Nano-emulgel is basically formed by admixing nanoemulsion system with a hydrogel matrix using both high and low energy methods. Various literatures have been reported for lipoidal nanocarriers in topical treatment suggesting reduced dose, improved percutaneous absorption and better bioavailability of lipophilic drugs with nano-emulgel delivery via topical route. Several approved marketed preparations are available that strongly support the stability of these nanocarriers in respect to its efficacy and safety. This supports the fact of using topical nano-emulgel system to deliver lipophilic drugs to overcome the sufferings from oral delivery and improved patient compliance. Therefore, it is suggested as a potential system that can be used for an effective management of psoriasis via topical route in near future. Dhaka Univ. J. Pharm. Sci. 20(2): 235-246, 2021 (December)

Cytotoxic Compounds Derived from Marine Algicolous and Spongicolous Endophytic Fungi: A Review

Endophytes have gained particular interest in the search of potential pharmaceutical candidates for a long time due to their diversity, species richness and bioprospecting nature. They generally produce the essential metabolites for their expansion inside the plant which is involved in various biotransformation processes of utilizing host nutrients and cell components to continue microbial growth, sustenance, and reproduction. In above processes, they produce a huge amount of both structurally and functionally diverse secondary metabolites for maintaining an effective symbiosis with hosts. These compounds are proven to have significant bioactive properties like antibacterial, antifungal, antiviral, anti-inflammatory, antioxidants, antitumor activities. Despite the proven significance, a little is exploited so far about endophytes. Particularly marine fungal endophytes which are the centre of attention in this review have gained much less importance. Due to unique environmental feature, fungal endophytes derived from marine environment offer vast diversity in different bioactive secondary metabolites. This review has focused on algicolous endophytes and bioactive secondary metabolites discovered during the last two decades. Particular importance has been given to cytotoxic and antimicrobial metabolites. Due to intensive studies during last several years, an extensive number of publications are now available on cytotoxic compounds derived from endophytic fungi of marine algicolous and spongicolous origin that have been summarized in this review. Dhaka Univ. J. Pharm. Sci. 20(2): 247-265, 2021 (December)

Evaluation of in vitro Dissolution Profile and Physicochemical Characterization of Polymer Based Formulations of Sparingly Soluble Rosuvastatin

Rosuvastatin (RVT) is a BCS class II antilipidemic crystalline drug, which exhibits low bioavailability due to its very poor aqueous solubility; therefore, it is challenging to develop a proper formulation of RVT. To enhance solubility and bioavailability of this API, an attempt has been made by implementing solid dispersion technique. Solid dispersion (SD) technique is a solubility enhancing technique where one or more active entities are dispersed in an inert medium (matrix or carrier) at solid state. In this study, different ratios of Kollicoat® IR (KIR) and Kollidon® 90F (KF90) polymers were used with API to prepare various formulations by physical mixing (PM) and SD approaches; here solvent evaporation technique was used whereas methanol was used as solvent which was completely evaporated from the homogenously dispersed system by placing in a water-bath at 60-65°C and then in oven for 30 minutes at 50 °C. Among the formulations, RVT-KF90 SD formulations showed the most promising result in in-vitro study in terms of drug release profile (78.04 – 99.21%) in comparison to pure RVT (63.1%) and physical mixing of RVT with those polymers. USP dissolution apparatus type II was used at 37°C ± 0.5°C with 50 rpm to conduct the in-vitro experiment. The experiment also unraveled that the dissolution of RVT improved with increasing the amounts of polymers. Subsequently, stability of the developed formulations was conducted by Fourier transforms infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) as well as scanning electron microscopy (SEM). The results obtained from FTIR ensured no involvement of any significant drug-excipient interaction. Moreover, the DSC study signified thermal stability at high temperature. Besides, the SEM micrograph illustrated homogenous distribution of RVT in the polymer and transformation of crystal-like RVT into amorphous formulations. Dhaka Univ. J. Pharm. Sci. 20(2): 199-211, 2021 (December)

Antioxidant, Analgesic and CNS Depressant Activities of Commelina diffusa Burm. f.

Commelina diffusa Burm. f. is a member of Commelinaceae family, which is widely grown in crop land and treated as a weed. This plant has several important medicinal properties which have not been studied extensively. In this study, the crude powder of C. diffusa whole plant was extracted with 95% ethanol and different solvent fractions (n-hexane, chloroform and methanol) were prepared from the crude extract by solvent-solvent partitioning. All these plant samples were subjected to bioassays for evaluating the antioxidant, central analgesic, peripheral analgesic and CNS depressant activities. The crude extract and its methanol soluble fraction showed mild free DPPH scavenging property with IC50 values of 98.49- and 84.77-μg/ml, respectively as compared to the standard ascorbic acid (IC50 = 2.67 μg/ml). In the analgesic activity test, the n-hexane fraction of C. diffusa at doses of 200- and 400-mg/kg body weight exhibited significant (p<0.05) central analgesic activity (tail flick test) in mice. Similarly, all the test samples showed statistically significant (p<0.05) reduction in abdominal writhing induced by acetic acid. C. diffusa showed significant CNS depressant activity which was measured by ‘open field test’ and ‘hole cross test’. Considering the potential bioactivities, the plant materials can be further studied elaborately to explore the activities of the purified compounds to aid in future drug development. Dhaka Univ. J. Pharm. Sci. 20(2): 159-166, 2021 (December)

CNS Depressant and Analgesic Activities of Thysanolaena maxima Roxb. Available in Bangladesh

In Bangladesh, numerous tribal people of Chittagong Hill Tracts have been using different parts of Thysanolaena maxima Roxb. for many years. The present study was designed to investigate CNS depressant and analgesic activities of methanol extract of the aerial parts of the plant in mice models. CNS depressant activity of the crude extract (200 and 400 mg/kg) was evaluated using open field, hole cross and thiopental-induced sleeping time tests using diazepam as the standard. Analgesic activity was determined using acetic acid-induced writhing and hot plate tests using diclofenac sodium as the standard. The extract showed dose dependent suppression of locomotion in open field and hole cross tests and exerted sedative action in thiopental induced sleeping time. In the open field and the hole-cross tests, maximum CNS depressant activity was observed at 90 min after administration of extract and the standard drug. The extract significantly induced the onset of sleep and prolonged the sleeping time in thiopental induced sleeping test compared to the control group. The extract produced significant (p < 0.05) analgesic activity by inhibiting writhing by 41.89% and 60.81%, at doses of 200 and 400 mg/kg body weight, respectively, which was comparable to the inhibition of diclofenac sodium (73.64%). Additionally, in hot plate test, the extract exhibited a significant (p < 0.05) increase in pain threshold in a dose dependent manner. The findings of the study are encouraging and demands further investigation of other bioactivities with isolation of pure compounds. Dhaka Univ. J. Pharm. Sci. 20(2): 227-233, 2021 (December)

Phytochemistry and In vitro Antimicrobial Activity of Five Plant Species against Nine Common Human Pathogens

Momordica charantia, Senna podocarpa, Senna alata, Ocimum gratissimum, and Sida acuta which have reportedly been used in folklore for the treatment of various diseases were studied for their antimicrobial activity. Crude methanolic extracts of the leaves were screened for phytochemicals after which they were tested in vitro for activity against clinical isolates of Staphylococcus aureus, Klebsiella oxytoca, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus subtilis, Enterobacter aerogenes, Aspergillus niger, A, flavus and Candida albicans. Phytochemicals present in the extracts included saponins, alkaloids, anthraquinones, tannins, flavonoids and cardiac glycosides. These extracts also showed varying degrees of activity against tested organisms at a concentration range of 15.6 to 500 mg/ml. However, S. acuta showed activity against P. vulgaris, E. aerogenes and As. flavus only. The MIC of the extracts against test organisms ranged from 31.25 to 250 mg/ml. The significant antimicrobial susceptibility of the plant extracts against gram positive bacterial pathogens and some pathogenic yeasts, may not be due to the presence and synergistic interactions of secondary metabolites found in these plant extracts. This would have implications in health, particularly in developing countries where a singnificant percentage of the population are still using traditional plant extracts for health care. Dhaka Univ. J. Pharm. Sci. 20(2): 139-148, 2021 (December)

Nickel(II)-Complex of Ceftibuten Dihydrate: Synthesis, Characterization and Thermal Study

Ceftibuten dihydrate is a semisynthetic, orally administered, third generation cephalosporin antibiotic which is effective against most of the pathogens causing infections in the respiratory tract. Complexation of ceftibuten dehydrate (Ligand, L) was performed with hydrated Ni(II) salt (Metal, M) in the ratio of 2:1 (L:M) in aqueous medium at 90 oC. The metal complex was then characterized by spectral techniques and thermal analyses. The FT-IR spectral data of metal complex suggested the monodentate bonding of metal ion to carboxylate group. Spectral evidence also supported the formation of five-membered ring via coordination of metal ion to β-lactam nitrogen and carboxylate group of parent drug. Thermal behavior of ligand and complex were studied. Thus, thermoanalytical (DSC and TGA) results also supported the formation of new metal complex, indicating the successful interaction of metal ion to ligand. Dhaka Univ. J. Pharm. Sci. 20(2): 219-225, 2021 (December)

Stability-Indicating UHPLC Method for the Determination of Desvenlafaxine: Application to Degradation Kinetics

This study was aimed to investigate the degradation behavior and physicochemical stability of desvenlafaxine using reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) system. The chromatogram was developed on Eclipse XDB-C8 column (150 x 4.6 mm, 5μm). The eluents were monitored through a photo diode array plus (PDA+) detector at 210 nm using an isocratic method with a flow rate of 1.5 ml/min. Mobile phase composition was 30:70 v/v mixture of 0.1 % trifluoroacetic acid (TFA) in water and methanol. Forced degradation studies were performed on drug substance of desvenlafaxine as per International Conference on Harmonization (ICH) prescribed stressed conditions (Q1A(R2) and Q1B) using hydrolytic (acidic, basic, and neutral), oxidative and photolytic methods. The drug substance was found highly labile to acidic (0.5 N hydrochloric acid, 18.65 % degradation in 2 hours at 70°C), basic (1.0 N sodium hydroxide, 11.01 % degradation in 12 hours at 70°C) and oxidative (3 % hydrogen peroxide, 17.05 % degradation in 2 hours at 50°C) stressed conditions, but a great resistance was observed towards dry heat (maximum degradation 0.27 % in 10 days from ambient to higher temperature, 80°C), moist heat (maximum degradation 0.25 % in 2 hours at 80°C and 75 % relative humidity) as well as in photolytic degradation (maximum degradation 0.23 % in 10 days at UV light of 315 - 400 nm). A pseudo-first order kinetic was followed in acidic, basic and peroxide degradation methods which paved a way to calculate the half-life of the drug substance desvenlafaxine under ICH mentioned stressed conditions. The results were also statistically analyzed and the % RSD values were compared with recommended guidelines. Dhaka Univ. J. Pharm. Sci. 20(2): 167-176, 2021 (December)