Ursolic acid inhibits NF-κB signaling and attenuates MMP-9/TIMP-1 in progressive osteoarthritis: a network pharmacology-based analysis.

Osteoarthritis (OA) is a degenerative joint disease, characterized by infiltration of monocytes into the synovial joint which promotes inflammation, stiffness, joint swelling, cartilage degradation and further bone destruction. The leaves of Ocimum forskolei have been used for inflammation-related disease management in traditional medicine. Additionally, the downregulation of NF-κB and the MMP/TIMP-1 ratio has been shown to protect against OA. The LC-HR-MS metabolic analysis of Ocimum yielded 19 putative compounds, among which ursolic acid (UA) was detected. Ursolic acid possesses significant anti-inflammatory effects and has been reported to downregulate oxidative stress and inflammatory biomarkers. It was tested on rats in a model of intra-articular carrageenan injection to investigate its efficacy on osteoarthritis progression. The UA emulgel exerted chondroprotective, analgesic and local anaesthetic efficacies confirmed via histopathological investigation and radiographical imaging. A network pharmacology followed by molecular docking highlighted TNF-α, TGF-ß and NF-κB as the top filtered genes. Quantitative real-time PCR analysis showed that UA significantly attenuated serum levels of TNF-α, IL-1ß, NF-κB, MMP-9/TIMP-1 and elevated levels of TGF-ß. Taken together, these results suggest that UA could serve as a functional food-derived phytochemical with a multi-targeted efficacy on progression of OA, regulating the immune and inflammatory responses, particularly, attenuating chondrocytes degeneration via suppression of NF-κB and MMP-9/TIMP-1. Accordingly, UA might be a promising alternative to conventional therapy for safe, easily applicable and effective management of OA.

In Vitro and Randomized Controlled Clinical Study of Natural Constituents' Anti-HPV Potential for Treatment of Plantar Warts Supported with In Silico Studies and Network Analysis.

The aim of this study is to evaluate the anti-HPV potential of a Moringa olifera Lam seed, Nigella sativa L. seed, and Musa Acuminata peel herbal mixture in the form of polymer film-forming systems. A clinical trial conducted in outpatient clinics showed that the most significant outcome was wart size and quantity. Compared to the placebo group, the intervention group's size and number of warts were considerably better according to the results. Chemical profiling assisted by LC-HRMS led to the dereplication of 49 metabolites. Furthermore, network pharmacology was established for the mixture of three plants; each plant was studied separately to find out the annotated target genes, and then, we combined all annotated genes of all plants and filtered the genes to specify the genes related to human papilloma virus. In a backward step, the 24 configured genes related to HPV were used to specify only 30 compounds involved in HPV infection based on target genes. CA2 and EGFR were the top identified genes with 16 and 12 edges followed by PTGS2, CA9, and MMP9 genes with 11 edges each. A molecular docking study for the top active identified compounds of each species was conducted in the top target HPV genes, CA2 and EGFR, to investigate the mode of interaction between these compounds and the targets' active sites.

Vitis vinifera leaf extract liposomal Carbopol gel preparation's potential wound healing and antibacterial benefits: in vivo, phytochemical, and computational investigation.

Vitis vinifera Egyptian edible leaf extract loaded on a soybean lecithin, cholesterol, and Carbopol gel preparation (VVL-liposomal gel) was prepared to maximize the in vivo wound healing and anti-MRSA activities for the crude extract, using an excision wound model and focusing on TLR-2, MCP-1, CXCL-1, CXCL-2, IL-6 and IL-1ß, and MRSA (wound infection model, and peritonitis infection model). VVL-liposomal gel was stable with significant drug entrapment efficiency reaching 88% ± 3, zeta potential value ranging from -50 to -63, and a size range of 50-200 µm nm in diameter. The in vivo evaluation proved the ability of VVL-liposomal gel to gradually release the drugs in a sustained manner with greater complete wound healing effect and tissue repair after 7 days of administration, with a significant decrease in bacterial count compared with the crude extract. Phytochemical investigation of the crude extract of the leaves yielded fourteen compounds: two new stilbenes (1, 2), along with twelve known ones (3-14). Furthermore, a computational study was conducted to identify the genes and possible pathways responsible for the anti-MRSA activity of the isolated compounds, and inverse docking was used to identify the most likely molecular targets that could mediate the extract's antibacterial activity. Gyr-B was discovered to be the best target for compounds 1 and 2. Hence, VVL-liposomal gel can be used as a novel anti-dermatophytic agent with potent wound healing and anti-MRSA capacity, paving the way for future clinical research.

Cholecalciferol-load films for the treatment of nasal burns caused by cauterization of the hypertrophied inferior turbinate: formulation, in vivo study, and clinical assessment.

Nasal turbinate hypertrophy is among the most common nasal obstruction disorders, affecting the patient's quality of life significantly. Endoscopic submucosal diathermy is a prevalent cauterization procedure for treating turbinate hypertrophy. Regrettably, the nasal burn associated with diathermy typically heals slowly causing facial pain and nasal bleeding and possibly resulting in synechiae formation. In the current study, we have developed, for the first time, a polymeric film loaded with cholecalciferol for local treatment of nasal burns. The casting method was used to prepare films of different compositions of polymers such as chitosan, polyvinyl alcohol (PVA), Carbopol 971p (CP971p), and hydroxypropyl methylcellulose (HPMC) as well as a plasticizer. Several characterizations were performed for the cholecalciferol-loaded films (e.g. weight, thickness, content uniformity, surface pH, folding endurance, disintegration time, and in vitro release) to select the optimal formulation. The optimal formulation (F4) displayed compatibility between the used polymers and the drug. In vivo animal study was carried out to assess the healing efficacy of the formulated cholecalciferol-loaded film. The rabbits treated with the cholecalciferol-loaded film demonstrated significantly higher mRNA expression of the growth factor TGF-ß and significantly lower mRNA expression of the proinflammatory cytokine TNF-α and IL-1ß compared to the plain film treated group and the untreated control group. A randomized, single-blinded, parallel, controlled clinical trial was conducted on 20 patients scheduled to undergo endoscopic submucous diathermy. The results of the clinical study demonstrated significant reductions in facial pain and nasal bleeding scores for the nostrils treated with cholecalciferol-loaded films in comparison to the nostrils treated with plain films. Furthermore, the endoscopic examination showed good healing for 95% of the cholecalciferol-loaded film-treated nostrils. In conclusion, the optimized film can be considered an opportune approach for enhancing the healing rate of nasal burns and thus reducing the downsides of the diathermy procedure.

Synthesis and molecular docking of new N4-piperazinyl ciprofloxacin hybrids as antimicrobial DNA gyrase inhibitors.

A series of N-4 piperazinyl ciprofloxacin derivatives as urea-tethered ciprofloxacin-chalcone hybrids 2a-j and thioacetyl-linked ciprofloxacin-pyrimidine hybrids 5a-i were synthesized. The target compounds were investigated for their antibacterial activity against S. aureus, P. aeruginosa, E. coli, and C. albicans strains, respectively. Ciprofloxacin derivatives 2a-j and 5a-i revealed broad antibacterial activity against either Gram positive or Gram negative strains, with MIC range of 0.06-42.23 µg/mL compared to ciprofloxacin with an MIC range of 0.15-3.25 µg/mL. Among the tested compounds, hybrids 2b, 2c, 5a, 5b, 5h, and 5i exhibited remarkable antibacterial activity with MIC range of 0.06-1.53 µg/mL against the tested bacterial strains. On the other hand, compounds 2c, 2e, 5c, and 5e showed comparable antifungal activity to ketoconazole against candida albicans with MIC range of 2.03-3.89 µg/mL and 2.6 µg/mL, respectively. Further investigations showed that some ciprofloxacin hybrids have inhibitory activity against DNA gyrase as potential molecular target compared to ciprofloxacin with IC50 range of 0.231 ± 0.01-7.592 ± 0.40 µM and 0.323 ± 0.02 µM, respectively. Docking studies of compounds 2b, 2c, 5b, 5c, 5e, 5h, and 5i on the active site of DNA gyrase (PDB: 2XCT) confirmed their ability to form stable complex with the target enzyme like that of ciprofloxacin.

Study of Different Local Treatments of Post COVID-19 Smell Dysfunction.

Introduction: This study was designed to differentiate between the impact of the topical nasal spray of corticosteroids, antihistamines, a combination of them, and normal 0.2% saline in treating patients with post-coronavirus disease 2019 (COVID-19) smell dysfunction. Materials and Methods: Patients with hyposmia or anosmia (n = 240), who recently recovered from COVID-19, were enrolled in this trial and were randomly assigned to four parallel groups. Group I (G1) received a combination of topical corticosteroid and antihistamine nasal spray (n = 60). Group II (G2) received topical corticosteroid nasal spray (n = 60). Group III (G3) received antihistamine nasal spray (n = 60). Group IV (G4) received 0.2% normal nasal saline nasal spray (n = 60). The treatments were used in all groups for 3 weeks. The sense of smell was assessed using the butanol threshold and discrimination tests. The smell tests were evaluated weekly for 3 weeks. Results: The mean age of the patients was 51.9 ± 7.1 years; moreover, 83.8% and 16.2% were male and female, respectively. The results of the smell tests in the first week significantly improved with those in the third week (P< 0.001). The greatest degree of improvement was found in the first group, followed by the second, third, and fourth groups. Conclusions: The results suggest the ability of combination therapy of corticosteroid and antihistamine nasal spray to manage post-COVID-19 hyposmia or anosmia; however, this combination therapy was not superior to corticosteroid nasal spray. Trial registration ID: UMIN000043537.

The effect of COVID-19 home quarantine on the psychological state of pharmacy students: a cross-sectional study.

BACKGROUND: Psychological morbidity has been documented in medical and pharmaceutical undergraduate students in different countries around the world. In this study, we examined the impact of coronavirus disease 2019 (COVID-19) home quarantine on the depressive psychological aspects of last-grade pharmacy students. METHODS: A cross-sectional study was conducted by the Department of Clinical Pharmacy, Faculty of Pharmacy, Deraya University, Egypt. Two hundred and sixty-eight last-grade pharmacy students were included in this study, and they completed a self-administered, pre-designed, anonymous questionnaire. The main outcome measures were the Hamilton Depression Rating Scale (HRS) and Patient Health Questionnaire-9 (PHQ-9), which were measured to screen for the symptoms of psychological depression and determine the degree of depression severity between the beginning and the end of the COVID-19 home quarantine period. Data entry and analysis were done using the Statistical Package for Social Science (SPSS) software version 26. Descriptive statistics were employed for analyses of the data, and categorical variables were described by frequencies and percentages. Bivariate and multivariable analyses were performed to examine relations between demographic data and psychological scales. The study protocol was approved by the Faculty of Pharmacy, Minia University Ethical Committee. RESULTS: A total of 268 students participated in this study (102 males and 166 females). The mean ± SD score of baseline HRS and HRS at the end of the study was 6.3 ± 4.45, 7.95 ± 5.36, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The mean ± SD score of baseline PHQ-9 and PHQ-9 at the end of the study was 4.35 ± 3.45, 5.37 ± 4.14, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The results showed that the COVID-19 home quarantine period led to a depressive psychological effect on the students in this study. CONCLUSIONS: Students' psychological depression causes morbidity and, in some cases, mortality. Psychological depressive problems were significantly associated with the COVID-19 home quarantine period, which calls for early intervention to solve it. Student counselling services must be more accessible and affordable to overcome this problem.

Anti-otomycotic potential of nanoparticles of Moringa oleifera leaf extract: an integrated in vitro, in silico and phase 0 clinical study.

Otomycosis is a serious superficial mycotic infection of the outer ear canal caused by some pathogenic species of Candida and Aspergillus. The infection remains a challenge to clinicians owing to the incomplete efficacy of market-available antifungal agents and high recurrence rates. The Moringa oleifera leaf ethanol extract showed efficacy against Candida albicans SC5314, compared to Nystatin® as a reference with MIC values of 7 and 718.33 µg ml-1, respectively. The extract was mixed with lecithin and chitosan to give Moringa core/shell giant nanoparticles, with a good zeta potential (+59.2 mV), a suitable entrapment efficiency (61%) and an enhanced release reaching up to 90% at 8 h. Clinical isolates from oomycote patients were identified via DNA sequencing as Candida parapsilosis, Aspergillus niger and Aspergillus flavus, and the effect of the prepared nanoparticles was tested against them via disk diffusion assay to give inhibition zones of 75, 55 and 55 mm, compared to Nystatin® with 35, 25 and 20 mm, respectively. Interestingly, patients treated with the Moringa-loaded nanoparticles experienced improvement within 1 week with no recurrence for more than 3 months. To have some insight into the bioactive components in the Moringa extract, LC-HRMS-based identification has been employed which led to the annotation of 27 compounds. Subsequent comprehensive in silico investigation suggested some alkaloids to be responsible for the activity targeting the fungal 14-α-demethylase enzyme (CYP51B). Our study revealed that Moringa extract-loaded nanoparticles attained an enhanced antifungal efficacy compared to Nystatin® and therefore they can be employed against invasive and drug-resistant otomycotic infections.

The Potential of Corchorus olitorius Seeds Buccal Films for Treatment of Recurrent Minor Aphthous Ulcerations in Human Volunteers.

Aphthous ulcers are very common disorders among different age groups and are very noxious and painful. The incidence of aphthous ulcer recurrence is very high and it may even last for a maximum of 6 days and usually, patients cannot stand its pain. This study aims to prepare a buccoadhesive fast dissolving film containing Corchorus olitorius seed extract to treat recurrent minor aphthous ulceration (RMAU) in addition to clinical experiments on human volunteers. An excision wound model was used to assess the in vivo wound healing potential of Corchorus olitorius L. seed extract, with a focus on wound healing molecular targets such as TGF-, TNF-, and IL-1. In addition, metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds was explored. Moreover, molecular docking experiments were performed to elucidate the binding confirmation of the isolated compounds with three molecular targets (TNF-α, IL-1ß, and GSK3). Additionally, the in vitro antioxidant potential of C. olitorius seed extract using both H2O2 and superoxide radical scavenging activity was examined. Clinical experiments on human volunteers revealed the efficiency of the prepared C. olitorius seeds buccal fast dissolving film (CoBFDF) in relieving pain and wound healing of RMAU. Moreover, the wound healing results revealed that C. olitorius seed extract enhanced wound closure rates (p ≤ 0.001), elevated TGF-ß levels and significantly downregulated TNF-α and IL-1ß in comparison to the Mebo-treated group. The phenotypical results were supported by biochemical and histopathological findings, while metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds yielded a total of 21 compounds belonging to diverse chemical classes. Finally, this study highlights the potential of C. olitorius seed extract in wound repair uncovering the most probable mechanisms of action using in silico analysis.

Insulin fast-dissolving film for intranasal delivery via olfactory region, a promising approach for the treatment of anosmia in COVID-19 patients: Design, in-vitro characterization and clinical evaluation.

The present work aimed to formulate intranasal insulin fast-dissolving films for treatment of anosmia in patients post COVID-19 infection. Variant films were prepared employing the casting method and using hydroxypropyl methyl cellulose and polyvinyl alcohol. The formulated films were investigated for insulin content, weight variation, surface pH, thickness, folding endurance and disintegration time. In vitro release study was conducted for the selected formulations (F6, F7, F8). A drug/polymer interaction was investigated in the optimized formulation (F7) employing Fourier transform infrared spectroscopy. Clinical study was accomplished for F7 on 20 patients. Sniffin's and olfactory discrimination tests were used for assessing patients. The formulated films displayed appropriate physical characteristics. F7 showed the shortest disintegration time (50 ± 7 s) and fastest release. It displayed compatibility between the drug and the used polymers. The results of the clinical study revealed a significant increase in the olfactory detection scores and olfactory discrimination values in the intervention group (7.9 ± 1.2, 6.7 ± 0.5 respectively) compared to placebo group (3 ± 0.8, 2.8 ± 1).. Intervention group showed significant differences between these scores before and after treatment while the placebo group did not display any significant differences. Thus, the optimized film can be considered as an auspicious approach for managing post COVID-19 anosmia.

New Acaciin-Loaded Self-Assembled Nanofibers as MPro Inhibitors Against BCV as a Surrogate Model for SARS-CoV-2.

BACKGROUND: SARS-COVID-2 has recently been one of the most life-threatening problems which urgently needs new therapeutic antiviral agents, especially those of herbal origin. PURPOSE: The study aimed to load acaciin (ACA) into the new self-assembled nanofibers (NFs) followed by investigating their possible antiviral effect against bovine coronavirus (BCV) as a surrogate model for SARS-COV-2. METHODS: ACA was identified using 1H-NMR and DEPT-Q 13C-NMR spectroscopy, the molecular docking study was performed using Autodock 4 and a modification of the traditional solvent injection method was applied for the synthesis of the biodegradable NFs. Different characterization techniques were used to inspect the formation of the NFs, which is followed by antiviral investigation against BCV as well as MTT assay using MDBK cells. RESULTS: Core/shell NFs, ranging between 80-330 nm with tiny thorn-like branches, were formed which attained an enhanced encapsulation efficiency (97.5 ± 0.53%, P<0.05) and a dual controlled release (a burst release of 65% at 1 h and a sustained release up to >24 h). The antiviral investigation of the formed NFs revealed a significant inhibition of 98.88 ± 0.16% (P<0.05) with IC50 of 12.6 µM against BCV cells. CONCLUSION: The results introduced a new, time/cost-saving strategy for the synthesis of biodegradable NFs without the need for electric current or hazardous cross-linking agents. Moreover, it provided an innovative avenue for the discovery of drugs of herbal origin for the fight against SARS-CoV-2 infection.

A New Approach for Dry Eye Management By Mucoadhesive In situ Gel of Vitamin B12: Formulation, In vitro and In vivo Assessment.

The commitment of the existent study was to develop a mucoadhesive in situ gel systems of vitamin B12 for the management of dry eye disease. The gels were prepared using pluronic F-127 and either of chitosan, carbapol 971P, sodium alginate, or hydroxy propyl methyl cellulose. Drug-excipients compatibility was investigated by means of differential scanning calorimetry and Fourier transform infrared spectroscopy. The gels were characterized for pH, clarity, gelling capacity, viscosity, and adhesion. In vitro release of vitamin B12 from the selected gels was investigated. In vivo effectiveness of the selected gel was determined in rabbit models using Schirmer's and fluorescein tests. The compatibility studies revealed the possibility of incidence of drug/polymer interaction in some formulations. F2-containing pluronic F127 and hydroxypropyl methyl cellulose showed the most appropriate physical characterization and in vitro release profile. The prepared gels showed prolonged drug release with drug release mechanism of combined diffusion and erosion. The in vivo study revealed good effectiveness of the prepared mucoadhesive in situ gel system of vitamin B12 in the treatment of dry eye disease that was comparable to that of the marketed drops.

A novel nasal co-loaded loratadine and sulpiride nanoemulsion with improved downregulation of TNF-α, TGF-ß and IL-1 in rabbit models of ovalbumin-induced allergic rhinitis.

PURPOSE: The work aimed to develop a co-loaded loratadine and sulpiride nasal nanoemulsion for allergic rhinitis management. METHODS: Compatibility studies were conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. Nanoemulsion formulations were prepared using soybean lecithin, olive oil and tween 80. Sodium cholate and glycerol were employed as co-surfactants. Nanoemulsions were assessed for viscosity, pH, droplet size, polydispersity index, zeta potential, electrical conductivity, entrapment, In vitro drug release and corresponding kinetics. Stability of the selected formulation was investigated. The biological effectiveness was evaluated in rabbit models of ovalbumin-induced allergic rhinitis by measuring TNF-α, TGF-ß and IL-1. RESULTS: Compatibility studies revealed absence of drug/drug interactions. Nanoemulsions exhibited > 90% entrapment efficiency. The selected nanoemulsion demonstrated small droplet size (85.2 ± 0.2 nm), low PDI (0.35 ± 0.0) and appropriate Zeta Potential (-23.3 ± 0.2) and stability. It also displayed enhanced in vitro drug release following the Higuashi Diffusion and Baker-Lonsdale models. The mean relative mRNA expression of TNF-α, IL-1 and TGF-ß significantly decreased from 9.59 ± 1.06, 4.15 ± 0.02 and 4.15 ± 0.02 to 1.28 ± 0.02, 1.93 ± 0.06 and 1.56 ± 0.02 respectively after treatment with the selected nanoemulsion formulation. CONCLUSION: The results reflected a promising potent effect of the combined loratadine and sulpiride nasal nanoemulsion in managing the symptoms of allergic rhinitis.

Topical Nano-Vesicular Spanlastics of Celecoxib: Enhanced Anti-Inflammatory Effect and Down-Regulation of TNF-α, NF-кB and COX-2 in Complete Freund's Adjuvant-Induced Arthritis Model in Rats.

BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that underlies chronic inflammation of the synovial membrane. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat RA. However, a long list of adverse events associated with long-term treatment regimens with NSAIDs negatively influences patient compliance and therapeutic outcomes. AIM: The aim of this work was to achieve site-specific delivery of celecoxib-loaded spanlastic nano-vesicle-based delivery system to the inflamed joints, avoiding systemic administration of large doses. METHODOLOGY: To develop spanlastic nanovesicles for transdermal delivery of celecoxib, modified injection method was adopted using Tween 80 or Brij as edge activators. Entrapment efficiency, vesicle size, ex vivo permeation, and morphology of the prepared nano-vesicles were characterized. Carbopol-based gels containing the selected formulations were prepared, and their clarity, pH, rheological performance, and ex vivo permeation were characterized. Celecoxib-loaded niosomes and noisome-containing gels were developed for comparison. The in vivo efficacy of the selected formulations was evaluated in a rat model of Freund's complete adjuvant-induced arthritis. Different inflammatory markers including TNF-α, NF-кB and COX-2 were assessed in paw tissue before and after treatment. RESULTS: The size and entrapment efficiency of the selected spanlastic nano-vesicle formulation were 112.5 ± 3.6 nm, and 83.6 ± 2.3%, respectively. This formulation has shown the highest transdermal flux and permeability coefficient compared to the other investigated formulations. The spanlastics-containing gel of celecoxib has shown transdermal flux of 6.9 ± 0.25 µg/cm2/hr while the celecoxib niosomes-containing gel and unprocessed celecoxib-loaded gel have shown 5.2 ± 0.12 µg/cm2/hr and 0.64 ± 0.09 µg/cm2/hr, respectively. In the animal model of RA, the celecoxib-loaded spanlastics-containing gel significantly reduced edema circumference and significantly suppressed TNF-α, NF-кB and COX-2 levels compared to the niosomes-containing gel, the marketed diclofenac sodium gel, and unprocessed celecoxib-loaded gel. CONCLUSION: The spanlastic nano-vesicle-containing gel represents a more efficient site-specific treatment for topical treatment of chronic inflammation like RA, compared to commercial and other conventional alternatives.

Bucco-Adhesive Film as a Pediatric Proper Dosage Form for Systemic Delivery of Propranolol Hydrochloride: In-vitro and in-vivo Evaluation.

OBJECTIVE: To formulate and assess bucco-adhesive films of propranolol hydrochloride for pediatric use. METHODS: Different films were formulated adopting mucin, polyvinyl alcohol, chitosan and carbopol. A drug/polymer compatibility study was conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. The prepared films were physically investigated for variation of weight, propranolol content, thickness, surface pH, proportion of moisture, folding endurance and mucoadhesion. In vitro drug release study and kinetic analysis of the corresponding data have been conducted. The optimized formulation was selected for a bioavailability study using albino rabbits and adopting a developed HPLC method. The pharmacokinetic parameters of the drug were calculated following administration of the optimized film and the corresponding marketed oral tablets to albino rabbits. KEY FINDING: The compatibility study revealed the absence of drug/polymer interaction. The film formulations had suitable mucoadhesive and mechanical properties. The optimized formulation exhibited reasonable drug release that followed Higuchi diffusion pattern. The calculated AUC0-8h presented an enhancement in the bioavailability of propranolol hydrochloride from the selected film formulation by 1.9 times relative to the marketed propranolol oral tablets. CONCLUSION: These findings support that propranolol hydrochloride bucco-adhesive film can be considered as a proper effective dosage form for pediatric delivery.

Vitamin B12 buccoadhesive tablets: auspicious non-invasive substitute for intra muscular injection: formulation, in vitro and in vivo appraisal.

Attempting to prepare a convenient bioavailable formulation of vitamin B12 (cyanocobalamin), 17 tablet formulations were prepared by direct compression. Different concentrations of hydroxypropyl methyl cellulose (HPMC), carbopol 971p (CP971p), and chitosan (Cs) were used. The tablets were characterized for thickness, weight, drug content, hardness, friability, surface pH, in vitro drug release, and mucoadhesion. Kinetic analysis of the release data was conducted. Vitamin B12 bioavailability from the optimized formulations was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neurotone® I.M. injection was used for comparison. HPMC (F1-F4), CP971p (F5-F8), and HPMC/CP971p (F12-F15)-based formulations showed acceptable mechanical properties. The formulated tablets showed maximum swelling indices of 232 ± 0.13. The surface pH values ranged from 5.3 ± 0.03 to 6.6 ± 0.02. Bioadhesive force ranged from 66 ± 0.6 to 150 ± 0.5 mN. Results showed that CP971p-based tablets had superior in vitro drug release, mechanical, and mucoadhesive properties. In vitro release date of selected formulations were fitted well to Peppas model. HPMC/CP971p-based formulations showed bioavailability up to 2.7-folds that of Neurotone® I.M. injection.

Vitamin B12-Loaded Buccoadhesive Films as a Noninvasive Supplement in Vitamin B12 Deficiency: In Vitro Evaluation and In Vivo Comparative Study With Intramuscular Injection.

This study aimed to formulate and evaluate vitamin B12-loaded buccal mucoadhesive hydrogel films. Various film formulations were prepared using chitosan and polyvinyl alcohol. The prepared films were characterized for thickness, weight variation, drug content, percentage moisture uptake and moisture content, surface pH, mechanical properties, in vitro release, and mucoadhesion. Vitamin B12 bioavailability from the optimized formulation was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neuroton® I.M. injection was used for comparison. The films had acceptable mechanical and mucoadhesion properties. The percentages of moisture content of the optimized formulation were 3.2 ± 0.95, whereas the percentage drug released was 98.59 ± 1.41% at the end of 40 min. FTIR revealed the incidence of drug/polymer interaction. Differential scanning calorimetry revealed the possibility of the dispersion of cyanocobalamin in a molecular state with complete amorphization in the polymers. The estimated AUC0-8h showed 1.5-fold increases in the bioavailability of cyanocobalamin from the optimized formulation compared with the marketed I.M. injection. These findings warrant that vitamin B12 buccal film formulation can be considered as an effective alternative portal with noninvasive and more convenient characteristics compared with the I.M. injection dosage form.