A comprehensive review on pharmaceutical cocrystal - a subtle technique for solubility enhancement
	Sayani Bhattacharyya, Archana Manjunath
	Page: 622 - 630
	[Abstract] [PDF]  Solubility enhancement of active pharmaceutical ingredients is a challenging field in the pharmaceutical industry. Poorly soluble drugs lack oral bioavailability. Several methods and excipients are employed in the solubility improvement process. The physical and chemical properties of the developed compound play a key role in solubility enhancement. Crystal engineering is a novel strategy to alter the physicochemical properties of the molecule without causing significant changes in its structural integrity. Cocrystals are single-phase or homogeneous crystalline structures composed of two or more compounds bound noncovalently with the active pharmaceutical ingredient in a definite stoichiometric ratio. The cocrystallization technique is effective in improving the problems associated with solubility, bioavailability, permeability, stability, hygroscopicity, flowability, and process ability. This review represents the concept, characterization, and application of cocrystal in a systematic way. The review focuses on the requisite and mechanism of cocrystal formation, different preparation methods of cocrystals, and stages of screening. The growing interest in this technique has led the regulatory bodies to implement the guidelines and a brief on regulatory perspectives is discussed here. The cocrystallization method establishes the proof of concept of its potential in the pharmaceutical field through increasing number of patents and market approval.

	Hepatotoxic effect of cadmium and available therapeutic options
	Tomilola Olaolu, Favour Jibulu, Rotimi Damilare
	Page: 631 - 637
	[Abstract] [PDF]  Hepatoxicity, also known as toxic hepatitis, is a condition, in which the liver becomes inflamed due to exposure to such substances as chemicals, medications, herbal products, or excessive alcohol consumption. Cadmium is a major environmental pollutant from agricultural and industrial sources and has been reported to induce hepatotoxicity. Cadmium can also be found in phosphate fertilizers, detergents, and refined petroleum products as an impurity and used industrially in the production of polyvinyl chloride product stabilizers and the fabrication of nickel-cadmium batteries. Cadmium can be absorbed into the human body through the gastrointestinal tract, respiratory, and dermal routes. Cadmium-induced hepatic damage is very much associated with oxidative stress through inactivation of the antioxidant enzymes, depletion of the glutathione concentration, and increase in mitochondrial-derived reactive oxygen species production. Several processes of ameliorating cadmium-induced hepatotoxicity include the use of orthodox medicine (ethylene diamine tetraacetic acid, dimercaptosuccinic acid, and dimercaptopropane sulfonate). Furthermore, the phytomedicinal approach has served as hepatoprotective agents to averts any damage due to oxidative stress caused by cadmium in the liver. Therefore, this review seeks to understand the hepatotoxic effect of cadmium and its amelioration by orthodox medicine and selected medicinal plants.

	Characterization of quality attribute and specification for standardization of acemannan extracted from Aloe vera for tissue regeneration
	Siriwan Seeleamngam, Polkit Sangvanich, Pasutha Thunyakitpisal, Vorasit Vongsutilers
	Page: 638 - 645
	[Abstract] [PDF]  Acemannan extracted from Aloe vera was well characterized as an acetylated mannose polysaccharide which have promising clinical profile for tissue regeneration. Quality aspect of acemannan is required to develop the herbal extract for practical industrial application and reliable therapeutic use. The research aim is to investigate the qualify attributes of acemannan that have impact on its safety and efficacy. Quality of three production batches of acemannan were evaluated based on ICH quality guidelines and pharmacopeial standard. The quality aspect of acemannan were determined by analytical technique including FT-IR, SEC-HPLC, RP-HPLC, GC, and loss on drying to ensure its identify and purity. The cell proliferation assay was determined to evaluate the potency of acemannan on tissue regeneration. The physicochemical characters of acemannan samples were consistency. Their identities confirmed by IR spectra and retention time. Molecular size distribution has shown that acemannan size below 100 kD may contribute to better activity as seen in cell proliferation assay and can be used to qualify acemannan potency. The purity profile of acemannan has indicates that contamination of impurities including aloin and residual solvent were within acceptable limits. Specification of acemannan as active pharmaceutical ingredient was established and can be applied for commercial use.

	Docking, synthesis of some novel flavonoid analogues, and their biological evaluation
	Ishwar Bhat K, Afiya Abdul Aziz, Abhishek Kumar, Vijaya Bhaskar K, Vijay Kumar M
	Page: 646 - 652
	[Abstract] [PDF]  Cancer remains a major class of morbidity and mortality despite basic and clinical research and trials of promising new therapies. In the current era, many drugs are marketed with flavonoid nucleus. Based on this information, this study aims to synthesize and screen flavones for their anticancer activity. Docking studies for cytotoxic activity of flavonoid derivatives targeting tankyrase enzyme were performed. A new series of flavonoid derivatives were prepared from chalcones. Chalcones were prepared between substituted benzaldehyde and 2-hydroxy acetophenone in the presence of potassium hydroxide as catalyst. The flavone derivatives were characterized based on IR, 1H NMR, and Mass spectral data. All the new compounds were subjected to antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl and nitric oxide free radical scavenging activity. Cytotoxic activity was evaluated by MTT assay on two different cell lines. The antioxidant result reveals the potent antioxidant activity of compounds f4 and f6. Compounds mf6 and mf11 possess moderate activity. Cytotoxic activity results revealed that compound f10 have moderate activity and compound f4 shows potent cytotoxic activity on both MCF-7 and Hep-G2 cell line. The in vitro results suggest that some of the compounds showed potent antioxidant and cytotoxic activity. Compound f4 may be a promising cytotoxic molecule.

	Preclinical study on hepatoprotective potential and antioxidant status analysis of the fruit extract of Rivina humilis L. (red pigeon berry) in rats
	Raju Asirvatham, Dinu George, P. A. Daisy, Dawn V. Tomy, G. Boby Johns
	Page: 653 - 659
	[Abstract] [PDF]  Hepatoprotective and antioxidant potential of hydromethanolic extract of Rivina humilis L. fruit (HMERH) was studied using the carbon tetrachloride (CCl4) and paracetamol (PCM) induced hepatotoxicity in Wistar rats. In both models, rats were divided into five groups having six rats in each. Group I received distilled water. Group II, disease control, Group III received 100 mg/kg of Silymarin. Group IV and Group V received 500, 1000 mg/kg of HMERH. All groups except Group II received treatment twice daily for 7 days. CCl4 (1.5 mL/kg, PCM (2 g/kg), p.o) were administered after the last dose. The degree of liver protection against toxicity was measured by estimating serum liver marker enzymes and protein. In addition, estimation of lipid profile, liver weight, and histopathological examination were done. Peroxidase (P), Catalase, glutathione, total protein, superoxide dismutase, and malondialdehyde were also estimated from the part of liver isolated. HMERH 500 and 1000 mg/kg treated groups showed a significant (P < 0.001) decrease in serum marker enzymes as well as total bilirubin levelswere also restored. It also stabilize and restored the lipid profile and endogenous antioxidant enzyme system. Hence, the hepatoprotective effect of HMERH 500 and 1000 mg/kg against CCl4 as well as PCM may possibly be mediated through antioxidant activity.

	Solubility enhancement of diacerein by spray drying technique, formulation development, and in vivo study
	Devidas G. Bachhav, Somashekhar S. Khadabadi, Leena P. Deore, Vilas B. Ghavate
	Page: 660 - 673
	[Abstract] [PDF]  Purpose: The aim of the present research was solubility and dissolution rate enhancement of diacerein by spray drying technique. Materials and Methods: Solid dispersions of diacerein with PEG-600, guar gum, poloxamer-188 and aerosil were prepared in different ratios using 32 factorial designs. FTIR, DSC, XRD and SEM were performed to study the interaction between drug and polymers and evaluated for in-vitro drug release study. Results and Discussion:In spray dried solid dispersion formulations there was decrease in crystallinity of diacerein, which leads to increase in dissolution of diacerein from solid dispersions. Diacerein 50 mg immediate release tablets formulated (using spray dried solid dispersion formulation which shows maximum drug release) by 32 factorial design to study effect of binder (PVPK-30) and disintegrant (Crospovidone) concentration on disintegration and dissolution of diacerein. Formulation showed better analgesic and anti-inflammatory activity and increase in bioavailability. Conclusion: Spray drying found to be effective technique to improve solubility, dissolution and bioavailability of poorly water-soluble drugs.

	Effect of spinach enriched with zinc and ω-3/Vitamin E treatment against fluoride-induced nephrotoxicity and bone calcification disturbance in rats
	Anfal Djouadi, Samir Derouiche
	Page: 674 - 681
	[Abstract] [PDF]  Objective: The goal of this study was to evaluate the alone or associated spinach, zinc, and ω-3/Vitamin E capacity to improve the renal function and bone calcification altered by fluoride in Wistar rats. Methods: In this study, 36 female Wistar albino rats were used; divided into six groups (n = 6); all groups except the control rats received orally 400 ppm of fluoride as sodium fluoride (NaF) in drinking water during 70 days and then four groups treated in the past 15 days by: Spinach powder, zinc, ω-3/Vitamin E, and spinach+ zinc + ω-3/Vitamin E. Some biochemical and histological markers were analysis. Results: Exposure to fluoride altered significantly (P < 0.05) the kidney function and structure, calcium status, and induced kidney oxidative stress by decreasing glutathione (56%) and increasing the Malondialdehyde (26%) levels compared to control. Treatments with spinach enriched with zinc and ω 3 modulate calcium levels, kidney oxidative stress status, and attenuate kidney histological disturbance Conclusion: Single or interactive treatments administration exhibited a significant normalized effect on bone calcification disturbance, histological alterations, and oxidative stress state in the rats kidney induced by NaF

	The efficacy of Vitamin B6 and alpha-lipoic acid in preventing levetiracetam depressant-like behavior in mice
	Azadeh Mesripour, Nasime S. Musavie
	Page: 682 - 687
	[Abstract] [PDF]  Background: Some antiepileptic drugs for instance levetiracetam cause depression in patients. Vitamin B6 is a cofactor involved in the neurotransmitter synthesis. α-Lipoic acid (ALA) is a mitochondrial cofactor that can prevent neuronal damage. The aim of this study was to evaluate the effectiveness of B6 and ALA for preventing levetiracetam depression in mice. Methods: Male NMRI mice (weighing 25 ± 3 g) were used. Levetiracetam (20 mg/kg), and pretreatments with ALA (20, 40 mg/kg), Vitamin B6 (100 mg/kg), or imipramine (10 mg/kg) as the control positive were all administered intraperitonealy for 14 consecutive days. The locomotor test and forced swimming test (FST) were performed on days 7 and 15 on same groups of animals, novelty suppressed feeding test (NSFT) was tested on day 16. Results: Immobility time in FST increased following levetiracetam administration (day 7, 166 ± 5.63s vs. control 135 ± 9.9s, P = 0.020; day15, 188 ± 6.45s vs. control 150 ± 9.55s, P = 0.0326). Pre-treatment with B6 significantly reduced the immobility time during FST (day 7, 109 ± 16.4s, P < 0.001; day 15, 124 ± 12s, P < 0.001 vs. levetiracetam alone), these changes were similar to imipramine, treatments did not change the locomotor activity. However, following ALA pre-treatment, the locomotor activity declined and neither of ALA doses reduced immobility time during FST. During NSFT, pre-treatment with B6, and ALA similar to imipramine decreased latency; B6 and ALA 20 mg/kg increased food intake compared to levetiracetam alone. Conclusion: While B6 pretreatment clearly prevented depressive-like behavior induced by levetiracetam, ALA 20 mg/kg showed antidepressant-like effect only in NSFT. Supplements are recommended for further evaluation to prevent depression comorbidity of antiepileptic drugs.

	Pharmacological evaluation of the antirheumatic activity of Callicarpa macrophylla leaves extracts by the estimation of hepatic, renal, and inflammatory markers
	Harjinder Kaur, Ganesh N Sharma, Mayur Bhurat
	Page: 688 - 695
	[Abstract] [PDF]  Background: Callicarpa macrophylla is used in traditional medicine to treat many disorders including analgesic, antipyretic and anti-inflammatory. The aim of this study is to investigate the ethanolic and ethylacetate extracts of C. macrophylla leaves against rheumatoid arthritis (RA). Materials and Methods: Acute toxicity was studied in vivo to determine the toxic doses of the ethanolic and ethyl acetate extracts. Anti-rheumatic activity was also evaluated in vivo using formaldehyde and Complete Freund’s Adjuvant models in Wistar rats. After that paw volume was evaluated by the digital Vernier caliper and blood sample was taken by retro-orbital plexus route for the estimation of hematological marker and plasma was used for the estimation of liver, kidney, and inflammatory markers. Further, the histopathology of the joint tissue was done by sacrificing the under experimented animals. Results: At 200 and 400 mg/kg, the ethanol and ethyl acetate extracts were the most active against RA. There was dose dependent reduction in paw volume in both arthritic models as compared to the arthritic control. The results of biological markers and hematological parameters were restored which were altered due to the progression of arthritis. All these results were further supported with histopathology of joint tissue where the extracts performed a reversal in inflammation and hyperplasia of synovium. The results of this study concluded that C. macrophylla ethanol extracts have better anti-arthritic activity in comparison with ethyl acetate extracts. Conclusion: The results of the present study support the traditional use of the leaves of C. macrophylla and may possibly serve as prospective material for further development of safe new pharmacoactive antirheumatic agents.

	Ascorbic acid-loaded poly(lactic-co-glycolic acid) nanoparticles incorporated into a polyacrylic acid gel as a promising tool for site-specific oral cancer therapy
	Nurul Ain Mohammad Hamdi, Ahmad Fahmi Harun Ismail, Muhammad Salahuddin Haris, Widya Lestari
	Page: 696 - 710
	[Abstract] [PDF]  Background: Chemotherapy is commonly used in oral cancer therapy, especially as the disease advances. However, it is associated with terrible adverse effects and the occurrence of chemoresistance which causes treatment failure. Thus, discovering a new potential anticancer agent and developing a safe, effective, and non-invasive drug delivery are necessary. Objective: The objective of the current study is to develop ascorbic acid-loaded poly(lactic-co-glycolic) acid (AA-PLGA) nanoparticles incorporated into polyacrylic acid gel intended to treat oral cancer. Materials and methods: Double emulsion solvent evaporation method was used to fabricate AA-PLGA nanoparticles. Optimization was carried out in the primary emulsion based on multilevel factorial design by testing at varying surfactant types and concentrations. The optimized nanoparticles formulation was further incorporated into different concentrations of polyacrylic acid gel, and compared with a mucoadhesive polyacrylic acid-based commercial product (Kin Care) as a reference. The optimized AA-PLGA nanoparticles were subjected to cytotoxic assay against the SCC-25 cell line. Results: For the optimized formulation, we observed particle size of 252 ± 2.98 nm, polydispersity index (PDI) of 0.151 ± 0.02, zeta potential of −20.93 ± 0.87 mV, and encapsulation efficiency of 69.73 ± 1.07%. Polyacrylic acid polymer with a strength of 1% was chosen as the optimum gelling agent for AA-PLGA nanoparticles-in-gel formulation. Cytotoxicity study of the optimized nanoparticle demonstrated significant (P < 0.05) reduction of cancer cell viability in a dose-dependent manner with a half-maximal inhibitory concentration value of 2.42 mg/mL. Conclusion: The results of the present study support the feasibility of AA-PLGA nanoparticles-in-gel formulation for oral cancer therapy

	Development of amino acid salt-based curcumin@lysine acetate co-amorphous system using liquid-assisted grinding for improved solubility and dissolution
	Udaykumar Patil, Snehal Rawal, Jidnyasa Pantwalawalkar, Sopan Nangare, Dilip Dagade, Pravin Patil, Namdeo R. Jadhav
	Page: 711 - 719
	[Abstract] [PDF]  Curcumin, multivalued phytoceutical, exhibits appreciable safety. However, its therapeutic utility is significantly compromised due to low aqueous solubility, and thus, poor absorption and low bioavailability become apparent. To surpass this limitation, the present work aims to develop amino acid salt-based curcumin@lysine acetate co-amorphous system for improved solubility and dissolution. Initially, screening of curcumin-amino acid mixtures was performed for saturation solubility assessment. Considering the outcome, lysine acetate was formulated to generate a co-amorphous mixture (COAM) by liquid-assisted grinding and evaluated for saturation solubility and different spectroscopical characterizations. Curcumin-lysine acetate COAM tablet formulation was developed by direct compression method and evaluated for appearance, thickness, hardness, weight variation, friability, drug content, disintegration, and in vitro dissolution studies. Further, curcumin-lysine acetate COAM and tablet formulation were screened for the accelerated stability study. Resultantly, curcumin-lysine acetate binary mixture demonstrated the highest saturation solubility among screened curcumin-amino acid binary mixtures that might be ascribed to the hydrotropic properties of lysine acetate. Moreover, 476-fold solubility enhancement in water was observed by curcumin-lysine acetate COAM. Later, the amorphization of the curcumin-lysine acetate COAM was confirmed using Fourier-transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction. COAM tablet formulation showed optimum evaluation characteristics with improved drug dissolution. Therefore, the amino acid salt-based co-amorphous system can be used for solubility and dissolution improvement of curcumin and other multivalued phytoceutical.

	Vegetable Oil-Based Cannabis: Its Cannabinoid Profiling and Photoprotective Effect on UVA-Irradiated Human Skin Keratinocytes
	Nur Alfan Muhammad Zen, Kwanlada Kobtrakul, Petlada Khositanon, Kittipong Sanookpan, Visarut Buranasudja, Sornkanok Vimolmangkang
	Page: 720 - 733
	[Abstract] [PDF]  Vegetable oils serve as affordable, non-toxic, and eco-friendly solvents for plant extraction. Chemical fingerprinting shows that vegetable oil-based cannabis has a cannabinoid profile similar to that of organic solvent-based cannabis. All samples possess antioxidative effects as they contain several cannabinoids and other unidentified compounds, with rice bran oil-based sample exhibiting the strongest effect. Tetrahydrocannabinol (THC) and cannabidiol (CBD) content in sesame oil-based and perilla seed oil-based cannabis differed significantly from that in virgin coconut oil (VCO)-based cannabis. In addition, THC and CBD content in all vegetable oil-based samples prepared using the heating and frying method differed significantly from that in samples prepared using conventional methods. The VCO-based cannabis was chosen to preliminarily test its photoprotective effect and antioxidant enzyme activity. The results showed that it can protect UVA-irradiated HaCaT cells. Pretreatment with VCO-based cannabis can promote Nrf-2/HO-1 signaling, thereby upregulating antioxidant enzymes and increasing the capacity of keratinocytes to detoxify oxidative insults. Herein, we present the first overview of the cannabinoid profile of vegetable oil-based cannabis, which can be used for quality control during the development of vegetable oil-based cannabis products. Furthermore, the skin photoprotective properties of oil-based extracts can provide supporting evidence for the formulation of cannabis-based skincare products.

	Determination of anti-herpes simplex virus type 1 activity of the air filter coated with silver ions using a modified method of ISO 21702:2019
	Mali Wirotesangthong, Ariya Khanboon, Kanyanat Piewpong
	Page: 734 - 739
	[Abstract] [PDF]  Background: Since severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 pandemic has emerged, various air membrane filters with antimicrobial agents have been explored and investigated for inactivating virus particles. Objectives: The purpose of this study was to determine an antiviral activity of the air filter coated with silver ions using the method of ISO 21702:2019. Materials and Methods: Herpes simplex virus type 1 (HSV-1), KOS strain, an enveloped virus causing skin, mucous membrane, and respiratory tract infection (RTI) were tested with the non-porous surface coated with or without silver ions (control filter) for 0, 24 h at 25°C. The viral infectivity titers were determined on Vero cells by a plaque assay. After 24 h, the silver filter showed high anti-viral effect with logarithmic reduction >3.91 or 99.92% reduction compared to that of the control filter. Validation of the method demonstrated that the filters were nontoxic, the cell was sensitive to the virus and the neutralizer could inactivate the antiviral activity. Conclusion: The air filter coated with silver ions possessed anti-HSV-1activity. Further study with other viruses causing RTI would be helpful for the prevention of viral spread.

	Application of concept mapping in telepharmacy model development for prescription filling at primary care clusters
	Nusaraporn Kessomboon, Siwapond Prasertsuk, Jirachaya Suttima, Nur-Ainee Korsem
	Page: 740 - 746
	[Abstract] [PDF]  Background: Although the Pharmacy Council of Thailand has announced a standard telepharmacy service procedure, there may be some details or limitations that are specific to the primary care cluster (PCC) in the real situation. Objective: This research aimed to create a telepharmacy service model for the PCC using concept mapping techniques. Methodology: Group discussions were held, each participant will submit their opinions and graded of importance and possibilities of each opinion. After that, the data obtained were statistically analyzed to create a concept mapping. Results: From the group discussion, (n = 10) can be concluded that the optimum telepharmacy services with five groups which are (1) communication technology, (2) coordination between PCC and pharmacies, (3) coordination between village health volunteers and pharmacists, (4) patient selection for the telepharmacy services, and (5) telepharmacy services management and all five groups had the same level of importance and possibility. Conclusion: The PCC telepharmacy services should bring all groups of opinions together in the actual practice. Concept mapping helps the researchers decide which point to focus on. In addition, it was found that both group discussions also contributed to the team development, according to Tuckman’s theory.

	Development of a Thai pharmacists’ cultural competency self-assessment scale
	Auttakrit Aunkaew, Puckwipa Suwannaprom, Siritree Suttajit
	Page: 747 - 758
	[Abstract] [PDF]  Objective: The objective of the study was to develop and evaluate a cultural competency assessment form for Thai pharmacists. Materials and Methods: The research was conducted in two phases. Phase 1 involved item development based on the Campinha-Bacote’s and the ACPP’s concept of cultural competency and the self-assessment of perceived level of cultural competence questionnaire. Seven experts assessed the content validity and face validity. The revised scale was tested for comprehension among 12 pharmacists using the think-aloud technique. Phase 2 constituted the scale development and scale evaluation. The Thai pharmacist cultural competency self-assessment (TPCCS) scale developed from Phase I was sent to randomly selected Ministry of Public Health Hospitals. A total of 241 pharmacists completed the online scale. Exploratory factor analysis and a reliability test were used to evaluate the data. Results: The developed TPCCS scale consisted of 79 items, 18 factors and 5 domains: awareness (23 items), skill (20 items), knowledge (20 items), encounter (11 items), and desire (5 items), explaining 31.5% of the total variance. The reliability of the five dimensions was between 0.8550 and 0.9217. Conclusion: Cultural competency is crucial for pharmacists as society evolves. The 79-item TPCCS scale has been systematically developed and has the potential to be improved for pharmacy workforce enhancement.

	Barriers and facilitators of wound care services provided by community pharmacists in selangor, malaysia: An exploratory qualitative study
	Hamidi Drahman, Mohd Shahezwan Abd Wahab, Mohd Faiz Mustaffa, Azyyati Mohd Suhaimi
	Page: 759 - 768
	[Abstract] [PDF]  Introduction: Community pharmacists (CPs) are often the first point of contact for patients to obtain health-related advice, including on wound management. Wound care services have been proposed as a community pharmacy practice area to be promoted in Malaysia. Objectives: This study aims to explore the types of wound care services provided by Malaysian CPs, and the factors associated with its provision. Methods: This study utilized the qualitative method to collect in-depth information about the barriers and facilitators associated with the provision of wound care services among a sample of CPs. Interview transcripts were analyzed using thematic content analysis. Results: Twenty-three CPs were recruited. Most of them were female (60.9%) and working at an independent pharmacy (69.6%). All CPs had provided counseling on wound care, and a minority provided wound care services in collaboration with other health-care providers, and first aid services. Barriers for the provision of wound care services among the CPs included the limited knowledge on wound, and the lack of a dedicated area. The perceived benefits of wound care services, and patients’ demand are some facilitators identified. Conclusion: Professional pharmacy bodies may utilize the findings from this study to develop strategies to further enhance wound care services by CPs.