Journal of Applied Pharmaceutical Research

Exploring the diverse therapeutic benefits of metformin: from anti-cancer to anti-inflammation and PCOS management

Sat, 31 Aug 2024 00:00:00 +0530

Background: Metformin is widely prescribed for type 2 diabetes mellitus and is recognized for its therapeutic benefits beyond glycemic control. This review summarizes current data on metformin's diverse roles in various therapeutic contexts, including treating polycystic ovarian syndrome (PCOS), anti-inflammatory effects, and cancer prevention. Method: This comprehensive examination highlights the multifaceted applications of metformin in modern medicine and its potential to enhance the treatment of inflammatory diseases, cancer, and reproductive disorders. Results and Discussion: Metformin's anti-inflammatory properties may benefit autoimmune disorders, neurological diseases, and cardiovascular illnesses. In women with PCOS, metformin aids in restoring menstrual regularity, inducing ovulation, and improving reproductive outcomes by enhancing insulin sensitivity, modulating ovarian function, and reducing hyperandrogenism. Additionally, emerging evidence suggests that metformin may reduce cancer incidence and mortality in diabetic individuals by modulating cellular metabolism, inducing apoptosis, and inhibiting tumor cell proliferation. Conclusion: Our review suggests promising evidence for metformin's role in cancer prevention, reducing inflammation, and managing PCOS. However, further research is required to identify patient subgroups that will benefit most from metformin therapy, elucidate its mechanisms of action, and optimize dosing regimens.

An update on phytoconstituents and pharmacological importance of Asparagus racemosus

Deepak Meher, Mithlesh Singh , Bibekananda Meher — Sat, 31 Aug 2024 00:00:00 +0530

Background: Asparagus racemosus (family: Liliaceae), is a well-researched traditional or ancient medicine in the Siddha, Ayurveda, and Unani systems. It is commonly known as Satawar, Satamuli, Satavari, and found at low altitudes throughout India. It contains bioactive metabolites such as fructo-oligosaccharides, polysaccharides, asparosides, shatavarins, sapogenins, racemosols, isoflavones, glycosides, mucilage, and fatty acids, while saponin is one of the main active constituents of asparagus.

Objective: Across the globe, Asparagus racemosus gained importance for its ethano-pharmacological value in curing various ailments. This review will outline the medicinal properties, uses, and value addition of Asparagus racemosus.

Methods: We have reviewed and retrieved the relevant information by probing the main keywords in online databases (PubMed, Scopus, Science Direct and Web of Science, etc.). Screening of relevant abstracts/ title and full papers were done to pick the suitable content based on the pharmacological profile of Asparagus racemosus.

Conclusion: The whole plant possesses pleiotropic therapeutic activity, antioxidant, anti-inflammatory, immunomodulatory, neuroprotective, nootropic, antidepressant, etc., without showing any remarkable side effects. It also treats stomach ulcers, diabetes, kidney disorders, and Alzheimer's disease, etc.

Solubility enhancement of etoricoxib using inclusion complexation with cyclodextrins: formulation of oro dispersible tablets by QbD approach

Sat, 31 Aug 2024 00:00:00 +0530

Background: The work was intended to enhance etoricoxib's solubility and dissolution rate and then develop oro-dispersible tablets for faster onset of action. Methodology: Inclusion complexes (ICs) of the drug were obtained with β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP β-CD) at ratios of 1:0.125, 1:0.25, 1:0.5, 1:1, and 1:2 (w/w). The selected cyclodextrin at appropriate drug carrier proportion was used to develop oro-dispersible tablets (ODTs) by direct compression, adding crospovidone as a super disintegrant. Phase solubility studies of etoricoxib were carried out by using multiple concentrations of β-cyclodextrin and hydroxypropyl β-cyclodextrin, i.e., 1 %, 2 %, 3 % w/v in distilled water at 37±2°C. Spectroscopic (FT-IR) and thermal analysis (DSC) techniques were employed to identify the drug-carrier interactions. Result: It showed that etoricoxib solubility improves with increasing hydrophilic carrier concentration. The Gibbs free energy values (ΔG˚_tr) are consistently negative, showing the solubility of etoricoxib. Significant drug carrier interaction in spectroscopic or thermal analysis was not found. Discussion: The ICs of drugs with β-CD and HP β-CD have successfully addressed the challenges of solubility enhancement and taste masking for etoricoxib. Conclusions: It is observed that the inclusion complexes formed by the kneading method using β-cyclodextrin (β-CD) at a 1:1 ratio and hydroxypropyl β-cyclodextrin (HP β-CD) at a 1:2 ratio can be used to improve dissolution. Hence β-CD (at a 1:1 ratio) is selected for the formulation of oro-dispersible tablets. ODTs offer more patient compliance and an alternative to available conventional tablets.

Formulation and in-vitro anticancer activity of nilotinib immediate release and ibrutinib sustained release pellets

Vishal Gupta, Jitendra Gupta — Sat, 31 Aug 2024 00:00:00 +0530

Background: Blood cancer is a significant contributor to mortality rates worldwide, and its prevalence is projected to rise on a global scale. This trend places considerable strain on healthcare systems and necessitates the expedited development of innovative treatments by pharmaceutical firms to remain competitive. Conventional pellets produce rapid plasma drug levels, but they might cause side effects, decrease effectiveness, and lead to poor therapeutic management. Ibrutinib and Nilotinib are employed to treat leukemia patients. Methodology: The current research aims to formulate, characterize, and anticancer effect of Nilotinib immediate release (NIR) and Ibrutinib sustained release (ISR) seal sugar-coated pellets. Micrometric properties estimated the characterization of the drug pellets, and surface morphology was estimated using scanning electron microscopy. Drug excipient compatibility studies, stability studies, and in-vitro drug release were accessed. Result & Discussion: The results of pellet formulations FNI-1 to FNI-5 showed that FNI-5 formulations showed 100±6.0 µm size and possessed excellent mechanical strength for giving pellets a good self-life; also, due to the higher drug content up to 99%, FNI-5 was the best suited for pellet formulation and because NIR showed 99.18 ± 2.12 drug release at 2h and ISR 99.03±3.74% up to 12h so that anticancer concentration maintained for prolonged period. The standard dose for cytotoxicity against the THP-1 cell line of Nilotinib was found to be 200 mg, and the maintenance oral dose of Ibrutinib was 140mg, with four times the intake of the drug up to 560 mg. In an in vitro study in FNI-5 (final formulation), the dose of Ibrutinib was reduced to 420 mg. Conclusion: A synergistic effect of Ibrutinib and nilotinib drugs was observed in the inhibition of cancer cell growth, with an IC50 value of 4.585 µg/mL

Formulation and evaluation of ointment containing hydroalcoholic extract derived from the bark of Moringa oleifera for wound healing activity in rat model

Sat, 31 Aug 2024 00:00:00 +0530

Background: This study aimed to assess the effectiveness of a hydroalcoholic extract derived from the bark of Moringa oleifera in facilitating the healing process of second-degree burns wounds. Moreover, a comprehensive assessment was carried out on standardized M. oleifera bark to ascertain its physiochemical characteristics, botanical compound layout, and antioxidant activity, all of which play a crucial role in its capacity to facilitate the healing process of burns. Methods: For 14 days, the efficacy of ointments containing a hydroalcoholic extract of M. oleifera bark at concentrations of 5% and 10% was evaluated for treating second-degree burns in rats. Additionally, histological analysis was conducted on skin tissue samples. Results: The M. oleifera bark extract exhibited TPC (52.56 mg/gm of dried extract) and TFC (84.33 mg/gm of dried extract) value along with antioxidant activity (IC₅₀ value of 0.98 µg/ml) for radical scavenging, in the presence of several phytochemicals. The most favorable outcomes were achieved using a 10% ointment composition, demonstrating a wound closure and tissue repair rate of 83.04 ± 0.89%, along with a noteworthy decrease in tissue oxidative stress indicators. Histological investigations have verified the wound-healing properties of M. oleifera bark extract. Conclusion: Due to its significant antioxidant properties and its capacity to create a moist environment for wounds, M. oleifera has the potential to serve as a natural treatment for burns. Additional clinical trials are recommended to validate the efficacy of M. oleifera bark extract as a therapeutic agent for wound healing.

Quantification of oteseconazole in rat plasma using LC-MS/MS and its application to pharmacokinetic study

Krishna Phani Chandra Susararla, Om Shelke, Neetu Shorgar — Sat, 31 Aug 2024 00:00:00 +0530

Background: Oteseconazole is a new molecule launched for human treatment. However, the information is not available in the public domain for analyzing blood samples. This study describes the method development and validation using LC-MS/MS to measure the concentration of Oteseconazole in rat plasma. Methodology: The analysis method was developed using a phenyl column, which was utilized to accomplish separation. Furthermore, the mobile phase was a combination of acetonitrile and 0.1% formic acid in water, with a ratio of 30:70 (v/v). The sample was introduced into the system at a 1.0 mL/min flow rate, and the injection volume was 10 μLand analyzed for five minutes using mass spectrometer +ESI mode. Results and discussion: MRM is used to quantify Oteseconazole and Posaconazole by analyzing the transitions of their respective m/z values. The concentration ranges of Oteseconazole were 5-100 ng/mL. The correlation coefficient of Oteseconazole was found to be 0. 999. HQC, MQC, LQC, and LLQC precision and accuracy were determined to be 98.60%, 98.69%, 96.11%, and 94.48%, respectively. Respectively, the accuracy recovery of Oteseconazole was determined to be 97.48%. In pharmacokinetic studies, it was observed that Oteseconazole exhibited an average AUC0-t value of 1386 ng-hr/ml and a Cmax value of 44.864 ng/ml in rats. Conclusion: The validated approach has effectively demonstrated the determination of pharmacokinetic parameters after the oral administration of Oteseconazole in Wister rats.

Formulation and development of bilayer tablet containing irbesartan and metformin hydrochloride for diabetic hypertensive patients

V D Gorde, Punit R Rachh, Someshwar Mankar, Saurin Amin, Prasad L Gorde — Sat, 31 Aug 2024 00:00:00 +0530

Background: Hypertension is a common complication of type II diabetes. The present research work aimed to develop bilayer tablets that would manage type II diabetes patients with hypertension. The prepared bilayer tablet has an immediate-release layer of anti-hypertensive irbesartan and a sustained-release (SR) layer of anti-diabetic metformin hydrochloride. The purpose of these bilayer tablets was to increase patient compliance by converting two separate monotherapy to single combination therapy. Methodology: Several ratios of polymers, including HPMC K100M, EC, Eudragit, and Guar gum, were employed to prolong the drug release for twelve hours. An immediate-release layer of irbesartan was prepared by spherical agglomeration. The physical properties, drug content, solubility profiles, release kinetics, and stability of prepared bilayer tablets were assessed. Results and Discussion: The examination of SR granules and bilayer tablets revealed outstanding packing qualities and excellent flow properties, with bulk and tapped densities ranging from 0.39-0.46 g/cm³ and 0.42-0.55 g/cm³, respectively. In vitro dissolution tests revealed that the immediate-release layer gave an initial burst of Irbesartan. Still, the sustained-release layer of metformin showed controlled drug release over 12 hours at greater polymer concentrations. According to stability testing, the bilayer tablets' physical properties, drug content, and dissolving profiles did not change significantly. Conclusion: The bilayer tablet combination of Irbesartan and Metformin exhibited desired physical features, controlled drug release, and stability. This formulation represents a viable treatment option for diabetic hypertensive patients, offering effective and consistent management of both disorders while improving patient compliance.

Rivaroxaban solid dispersions for dissolution enhancement and formulation of mouth disintegrating tablets

Sat, 31 Aug 2024 00:00:00 +0530

Background: Work is carried out to improve rivaroxaban's dissolution rate (DR) and develop mouth-disintegrating tablets for rapid onset of action. Objectives: The work objective was to improve the dissolution rate of rivaroxaban using PEG 6000 by preparing its solid dispersions (SDs) further to prepare mouth-disintegrating tablets (MDTs). Methods: Methods like physical mixing, melting, and solvent evaporation were used to prepare SDs at 1:0.5, 1:1, and 1:1.5 w/w ratios of rivaroxaban with PEG 6000 were prepared. Differential scanning calorimetry (DSC) and Infrared spectroscopy (IR) were used to characterize the SDs. The selected solid dispersion at an appropriate drug: carrier ratio was used to develop MDTs by direct compression, using super disintegrants. Results: The SDs show improved solubility and rate of dissolution. SDs developed using a melting or solvent evaporation technique showed a more than two-fold increase in dissolution rate. In the dissolution study, after 60 min, the pure drug dissolved 45 %, while the prepared SDs showed almost more than 90 % within the same period. No significant drug carrier interaction was observed in the IR and DSC studies. However, minor shifts in peak values were observed for the characterization of functional groups in the drug structure. Conclusions: Formulation of solid dispersions of the drug with PEG 6000 is a successful approach for the dissolution rate improvement of rivaroxaban. This work for dissolution rate improvement of rivaroxaban using PEG 6000 showed significant improvement in dissolution rate at a 1:1 w/w ratio prepared by solvent evaporation method, which was further selected for mouth disintegrating tablet formulation.

Design, development, and optimization of sumatriptan loaded ethosomal intra-nasal nanogel for brain targeting

Nagadivya Nerella, Bakshi Vasudha — Sat, 31 Aug 2024 00:00:00 +0530

Background: Sumatriptan is one of the most essential drugs for treating migraine. However, dosage-related side effects are still a worry despite its 14 % oral bioavailability and recurrence of migraine-associated diseases. Methodology: The fundamental focus of the study is to develop the sumatriptan intra-nasal nano-ethsomal gel by film hydration technique with the aid of QbD principles that govern the varied compositions and blends of polymers like HPMC K100M and Phospolipon 90G to develop a sustained release dosage form. Results and discussion: The preliminary FT-IR and DSC studies revealed no interactions between the drug and their physical mixtures. The present study considered three observable responses: vesicle size, zeta potential, and percent drug release after 24 h, taken into consideration during the optimization of the ethosomal formulations utilizing 3² central composite designs (CCD). The vesicle size (122.23 nm), zeta potential (-40.2 mV), and drug release percentage (92.61 %) for all formulations were seen in the F12 batch after 24h. The p-XRD and SEM studies indicated that the nano-ethosomal gel was stable. The stability studies indicated the preparation of a more stable formulation for the parameters under the study protocol. Conclusion: Using a novel intra-nasal brain targeting approach by adapting the film hydration technique, the current issues might be addressed, and the drug's duration of residence at the absorption site uptake substantially increase. To efficiently modify the drug's residence through the intra-nasal route, this work focuses on developing a nano-ethosomal gel loaded with sumatriptan.

Bioanalytical method for the simultaneous estimation of atoltivimab, maftivimab and odesivimab in rat plasma by LCMS/MS and its application to a pharmacokinetic study

Ibrahim Baje Syed, Madhavi Nannapaneni — Sat, 31 Aug 2024 00:00:00 +0530

Background: A quick, accurate, reproducible, and straightforward liquid chromatography-tandem mass spectrometry(LC-MS/MS) system employing Atoltavimab, Maftivimab, and Odesivimab as an internal standard for Zanamivir quantification was achieved. Zanamivir is a neuraminidase inhibitor that effectively treats influenza caused by influenza A and B viruses. Methodology: Whenever we use the Kinetex C-18 column, all HPLC parameters and conditions are obeyed, so we use this column. Separation was performed on a Kinetex C18 column (100 mm x 4.6 mm, 2.6µm) using isocratic elution with a buffer containing 1mL of formic acid in 1Lit of water and a mobile step consisting of a 40:60 v/v mixture of two elements, buffer and acetonitrile, with a flow rate of 1mL/min at 30⁰C temperature was used. Results & Discussion: We used different stationary phases in the optimization process, such as C18, C8, and CN-propyl. Using a kinetex C18 column with dimensions of (100 mm x 4.6 mm, 2.6 µm) connected to a PDA detector, we obtain strong peak shapes of Atoltivimab, Maftivimab, and Odesivimab from various trials. Flow rates in the mobile process were set to 1 mL/min. Conclusion: Atoltivimab, Maftivimab, and Odesivimab analysis was completed in 7 minutes over a good linear concentration range of 5ng/mL to 100ng/mL (r² = 0.999), 5ng/mL to 100ng/mL (r² = 0.999), and 5ng/mL to 100ng/mL (r² = 0.9998). The findings of the precision and recovery studies are within the appropriate range.

The potential effect of peel extracts of banana varieties: an in-vitro assessment

Sat, 31 Aug 2024 00:00:00 +0530

Background: Assamese cuisine is known for its use of kolakhar, a traditional ingredient; Rhizome, the skin and stem of bananas, can be used to make it. An ash filter from a banana tree is used to produce antacids. The word: kol” or “kola” is a local term for banana. In Assam, India, kolakhar is a common food additive and traditional ingredient. Method: Water is filtered through banana tree ashes to create this. The banana peel is burned after it has been dried. The ash is subsequently blended with water and left overnight. The mixture is filtered through a fine cloth once the ash has settled to the bottom of the container by the following morning. Several studies were carried out by evaluating the preparation of peel extract, Physicochemical parameters, antioxidant activity, etc. followed by some analytical methods to find the biologically active components, potential uses, and additional benefits of banana peels beyond what they currently serve as waste products. Finally, an antimicrobial study was performed by using the disc diffusion method. In this study, 4 different types of banana species investigated sought to determine the antioxidant capacity, antimicrobial activity, FT-IR, and UV to determine which one is better. Result: The physicochemical parameters, analytical technique, and assay provide an overview of the chemical characteristics, phytoconstituents, and food safety of kolakhar, which contribute to its unique properties in both traditional medicine and culinary applications. Conclusion: In conclusion, depending on the banana type used, banana peel extracts exhibit considerable promise as organic antioxidants and antibacterial agents. Therefore, considering all parameters, we obtained various potential effects from this study. The results are discussed with a graphical representation of the banana peel extract.

Optimization and evaluation of nebivolol hydrochloride loaded transferosomes using Box-Behnken experimental design

P V Shelke, Punit R Rachh, Someshwar Mankar, Saurin Amin, Deepak Jain — Sat, 31 Aug 2024 00:00:00 +0530

Background: This study optimizes and evaluates transferosomes containing Nebivolol Hydrochloride to enhance the drug's bioavailability and therapeutic efficacy. Ultra-deformable vesicles called transferosomes help to increase drug administration via the skin. Methodology: Using a thin-film hydration technique, beta-blocker Nebivolol Hydrochloride, which has antihypertensive properties, was added to transferosomes. To attain the ideal vesicle size (between 200 to 300 nm), entrapment efficiency, and deformability, the formulation was adjusted by adjusting the amounts of phosphatidylcholine, Span 80, and hydration time using a Box-Behnken experimental design. Particle size analysis, zeta potential measurement, and in vitro drug release tests were performed to characterize the transferosomes. Results and discussion: The optimized formulation demonstrated notable deformability, an entrapment effectiveness of 50%, and a vesicle size of 265 nm. The Box-Behnken design made it easier to evaluate the interactions between variables systematically. In vitro drug release studies showed a drug diffusion that persisted for a whole day, suggesting that transferosomes may have long-lasting therapeutic effects. Stability studies at room temperature and accelerated conditions over six months confirmed the formulation's robustness. Conclusion: The results imply that Nebivolol Hydrochloride transferosome-based delivery may be a viable strategy for improving the drug's bioavailability and effectiveness, as nearly 100% of drugs diffuse within 24 hr, perhaps leading to a breakthrough in the management of hypertension.

Treatment with Terminalia chebula (retz.): possible mechanism of inhibition of spermatogenesis and fertility in albino mice

Prakash Chandra Gupta, Laxmi Yadav — Sat, 31 Aug 2024 00:00:00 +0530

Background: There has been a continued effort to develop an effective male contraceptive of plant origin due to its ready availability, cost-effectiveness, and fewer side effects. The present study has evaluated the mechanism of inhibitory action of Terminalia chebula Retz. (T. chebula; family: Combretaceae) on spermatogenesis and fertility in albino mice after oral administration of the aqueous bark extract (100, 300, and 500 mg/kg BW daily) of T. chebula for 35 d. Methodology: The effects of the Terminalia treatment on various reproductive endpoints such as sperm parameters, testis histology, activities of 3ß- and 17ß-HSDs, immunoblot expressions of StAR and AR proteins, immunostaining of AR, serum testosterone level, LPO level, activities of SOD and catalase, and fertility indices were investigated. Toxicological and recovery studies have also been performed. Results: Testes in Terminalia-treated mice showed nonuniform histologic alterations. Sperm parameters, activities of 3ß- and 17ß-HSDs, immunoblot expressions of StAR and AR proteins, immunostaining of AR, and serum testosterone level were adversely affected, though activities of SOD and catalase were unchanged. Libido remained unaffected, but fertility was inhibited markedly in treated males without signs of toxicity. By 42 d of treatment discontinuation, Terminalia-induced deviations in the reproductive endpoints recovered to control levels. Conclusion: The results of the present study indicate that T. chebula treatment reversibly inhibits spermatogenesis and fertility without signs of toxicity. Further, antifertility effects result from diminished production of testosterone due to Terminalia-mediated inhibition of testicular steroidogenesis.

Pharmaceutical development of etodolac transfersomal gel for topical drug delivery system in rheumatoid arthritis

Ashwini Bachhav, Prashant L Pingale, Chandrashekhar D Upasani — Sat, 31 Aug 2024 00:00:00 +0530

Background: Transferosomes provide delivery of the drug into systemic circulation via the skin as a topical delivery system. So, this study started with the objective of formulating Etodolac transfersomal gel to enhance its skin permeation. Methodology: A total of nine transferosomes (ET-1 to ET-9) containing lecithin, different grades of span and tween, were successfully prepared using a rotary film evaporator. Results and Discussion: After primary evaluation, results were as particle sizes ranged from 222 to 421 nm, zeta potential shows results from –18.50 to –62.53 mV with PDI values 0.254 to 0.303, and the entrapment efficiency (EE%) of Etodolac in the transferosomes ranged from 54.15% to 80.25%. Additionally, the transfersomes formulations were included in carbopol 940 gels (ETC-1 to ETC-9 and EC-0 without transferosomes) and assessed for various characteristics like color, pH, homogeneity, spreadability, viscosity, and in vitro drug release study. Optimized formulation (ET4 and ETC4) underwent further analysis using SEM, TEM, DSC, FTIR, XRD, ex vivo skin permeation, skin irritation and in vivo studies. The in vivo results were compared. % edema inhibition maximum was observed with optimized transfersomal gel formulation (ETC4) as compared to the marketed formulation and plain Carbopol gel when the study was completed after 8 hrs. Conclusion: After this research, it is suggested that Etodolac Transfersomal gel (ETC4) can be considered as an alternate drug carriers system for topical delivery and it could be used to treat Rheumatoid Arthritis

Formulation and evaluation of phytosomes containing bioactive from Carica papaya seeds

Rima R Patil, Prashant L Pingale, Chandrashekhar D Upasani — Sat, 31 Aug 2024 00:00:00 +0530

Background: Papaya seeds are a rich source of proteins, fat, fibers, vitamins, minerals, monounsaturated fatty acids, polyphenols, and powerful antioxidants like flavonoids. Low solubility limits the absorption and bioavailability of herbal constituents. Hence, phytosomes of Papaya seed extract were formulated to enhance its solubility and bioavailability. Methodology: Papaya seeds were extracted using ethanol as solvent, and all the phytoconstituents present in the extract were assessed during the phytochemical screening and LC-MS analysis. In-vitro antidiabetic activity pure extract was determined by alpha-amylase and alpha-glucosidase enzyme inhibitory assay. The phytosomes of extract were formulated using the lipid thin film formation method and Soya lecithin and Cholesterol as lipids. The formulated phytosomes were analyzed for parameters such as particle size, zeta potential, encapsulation efficiency, percent drug content, and In-vitro dissolution study. The chemical nature of the formulation was studied using FTIR analysis and powder X-ray diffractometry. Thermal stability of phytosomes analyzed with the help of Differential Scanning calorimetry. Results: LC-MS identified 16 phytoconstituents. In-vitro antidiabetic activity showed 59.97% and 51.17% inhibition of enzymes alpha-amylase and alpha-glucosidase, respectively. The encapsulation efficiency of the optimized formulation was 88.41±0.91% with a particle size of 188.0±53.7nm. TEM images of formulation confirm the formation of phytosomes. FTIR, DSC, and Powder X-ray diffractometry showed no unwanted peaks. The in vitro dissolution study showed 89.26±1.05% CDR of phytosome, while the extract showed 47.78±0.59% CDR. Conclusion: Evaluation results of phytosomes suggest that this formulation can be used as an effective herbal antidiabetic formulation