International Journal of Pharmacy and Pharmaceutical Sciences

OPTIMIZING TRANSDERMAL PATCH FORMULATION FOR ENHANCED DELIVERY OF RIVAROXABAN: A COMPREHENSIVE DESIGN OF EXPERIMENTS APPROACH

RAMA RAO NADENDLA — 2024-12-01

Objective: To optimize Trans Dermal Patches (TDPs) of rivaroxaban using Poly Vinyl Pyrrolidone (PVP K30) and Hydroxypropyl Methyl Cellulose E50(HPMC E50) as hydrophilic polymers, Propylene Glycol(PG) as a plasticizer, and permeation enhancer.

Methods: TDPs were crafted using a solvent casting technique with a 2-level, 3-factor factorial design. These patches were assessed for thickness, folding endurance, in vitro drug release, drug content, and moisture uptake and loss. An 8-stage diffusion cell apparatus facilitated in vitro drug release testing. The independent variables were HPMC E50, PVP K30, and PG. The change in the concentration of these independent variables resulted in the optimization of the transdermal patch. The dependent variables were the thickness, folding endurance, and in vitro diffusion.

Results: The patch thickness ranged from 0.311±0.3 to 0.334±0.6. Folding endurance ranged from 58±0.7 92±6. The in vitro drug release ranged from 52.36% to 95.58%. The percentage drug content ranged from 83.58±0.4 to 95.26±0.5. The percentage of moisture content absorbed ranged from 21.36±0.13% to 25.54±0.26%. The percentage of moisture lost ranged from 1.01% to 2.31%.

Conclusion: PG increased the release of rivaroxaban because it permeated the membrane. HPMC E50 is highly soluble. Thus, rivaroxaban patches are potentially suitable transdermal drug delivery systems.

AN OBSERVATIONAL STUDY OF PERIPHERAL NEUROPATHY IN DIABETES PATIENTS ON METFORMIN THERAPY AND THE ROLE OF VITAMIN B-12 SUPPLEMENTATION

HARITHA PASUPULATI — 2024-12-01

Objective: This study aims to assess the prevalence of peripheral neuropathy in diabetic patients on metformin therapy using the Douleur Neuropathique 4 (DN-4) scale, explore the relationship between long-term metformin use and serum vitamin B-12 levels, and identify how metformin contributes to neuropathy. Additionally, it seeks to raise awareness about the importance of vitamin B-12 monitoring and supplementation for improving patient quality of life.

Methods: An observational study was conducted involving diabetes patients on metformin therapy. Data were collected on patient demographics, clinical characteristics, and vitamin B-12 levels. Peripheral neuropathy was assessed using the DN-4 questionnaire. Correlations between metformin duration, dosage, vitamin B-12 levels, and neuropathy prevalence were analyzed.

Results: The results indicated that the majority of the study population were male (61.2%) and aged 51-60 years (41.8%), with a majority proportion residing in urban areas (74%). A significant finding was that Peripheral neuropathy was prevalent in 44.8% of patients, with 51.5% exhibiting vitamin B-12 deficiency. Furthermore, the study identified a high prevalence of peripheral neuropathy with a significant correlation between longer metformin use and increased neuropathy (r =0.9372), additionally, a strong negative correlation between metformin dosage and Vitamin B-12 levels (r=-0.9189) highlighted the risk of deficiency with higher doses.

Conclusion: The study underscores the critical role of monitoring and supplementing vitamin B-12 in diabetes patients on metformin therapy to mitigate peripheral neuropathy. Regular screening and proactive supplementation could potentially reduce neuropathic complications associated with long-term metformin use.

SYNTHESIS AND EVALUATION OF A COUMARIN SCHIFF-BASE FOR IN VITRO ANTIBACTERIAL ACTIVITY AGAINST STAPHYLOCOCCUS AUREUS

SHREYA SHET — 2024-12-01

Objective: 44 novel Schiff bases of aminated 4-methylumbelliferones were designed and subjected to in silico evaluation of activity against S. aureus, with Dihydrofolate Reductase (DHFR) as the target. The top-scoring compounds (as per binding affinities) were subjected to drug-likeness and ADMET evaluation. Overall assessment of the binding affinities, drug-likeness and ADMET profile (especially toxicity) suggested that the derivative, BVSSS22 was found to be the most promising Schiff base (even when compared to the standard, Trimethoprim). Hence, the objective was to synthesize BVSSS22 and evaluate it for in vitro activity against S. aureus.

Methods: BVSSS22 was synthesized, characterized via melting point, TLC, and spectral data acquisition (ATR-IR, NMR, and HRMS), and evaluated for in vitro antibacterial activity against S. aureus using the agar-well diffusion method, with Trimethoprim as the standard (n=3).

Results: BVSSS22 was successfully characterized, and the in vitro antibacterial assay showed that BVSSS22 possessed zones of inhibition, where at 400 µg/ml, the zone of inhibition was slightly less than that of trimethoprim (18.33±0.57 mm v/s 17.33±1.15 mm).

Conclusion: The results show that BVSSS22 is a potent and safe drug candidate for anti-S. aureus action. However, it can be evaluated at a concentration higher than 400 µg/ml or undergo further structural optimization to enhance its in vitro potency to surpass that of Trimethoprim.

POINT PREVALENCE SURVEY OF ANTIMICROBIAL CONSUMPTION IN A TERTIARY CARE HOSPITAL OF NORTH EAST INDIA

MUKUNDAM BORAH — 2024-12-01

Objective: The study was conducted to quantify antimicrobial utilization and determine the patterns of antibiotic use in Indoor patients and ICUs of the hospital.

Methods: The Point Prevalent Survey (PPS) was conducted in a core “National Antimicrobial Consumption Network site” as a part of the National Centre for Disease Control-WHO project “Point prevalence survey of antimicrobial consumption at healthcare facilities.” The study was conducted as per the “WHO Methodology for PPS on Antibiotic use in hospitals” in March, 2022. Altogether, 1396 eligible patients were admitted during the survey period, and 1109 patients were included in the survey. Data were collected using a predesigned and pretested questionnaire in separate hospital, ward and patient forms.

Results: The prevalence of antibiotic use during the study was 79.44%. On an average, 1.39 antibiotics were in use per patient and only a minor fraction of (1.5%) patients received definitive therapy. Parenteral route of administration (92.72%) was mostly used for administration of antibiotics. The most common indication for antibiotic use was found to be surgical prophylaxis (30.66%). There were 154 antibiotic prescriptions in the 'Not Recommended' category. Double gram negative and double anaerobic cover accounted for 25% and 8.3% respectively of the total prescriptions.

Conclusion: Empirical use of antibiotics is common and lack of utilisation of antimicrobial susceptibility testing services requires urgent interventions. Routine monitoring of antibiotic use is recommended to improve the current scenario of antimicrobial consumption.

ACUTE TOXICITY STUDY OF ARSENICUM ALBUM IN WISTAR ALBINO RATS

MONISHA A. — 2024-12-01

Objective: In India, homeopathic medicines derived from arsenic trioxide, such as Arsenicum album (A. album), are used to treat COVID-19. Many of the Arsenicum album's adverse events during the COVID treatment led to drug discontinuation. Nonetheless, Ayurvedic, Yoga and Naturopathy, Unani, Siddha, and Homoeopathic (AYUSH) medicine prescribes it. Researching Arsenicum album's toxicity is now essential since it will help decide whether or not the drug can be utilized during treatment.

Methods: Acute oral toxicity was performed in Wistar Albino Rats to find out the effects of Arsenicum album in various organs. Rats were divided into three groups: Group A (control), Group B (Arsenicum album 1000μl/100g) and Group C (2000μl/100g). A Single bolus dose of Arsenicum album was given orally and the study period was conducted for 14 d. The rats were subsequently sacrificed on the 15th d and biochemical and histopathological studies were done.

Results: The acute oral toxicity study showed median Lethal dose (LD50) was greater than 2000μl/100g for Arsenicum album. Biochemical analysis showed a significant increase in HDL level in Group C (2000μl/100g) compared to Group A (control) and Group B (1000μl/100g). [P<0.05]. Blood glucose, when compared to Group A (control) is increased in both groups B and C but statistically not significant (p>0.05). When compared to Group A (control) there is no significant change in blood urea level in Groups B and C (p>0.05). Serum creatinine is increased in Groups B and C compared to Group A (control) but statistically not significant (p>0.05). LDL cholesterol is increased in groups B and C compared to Group A (control) but statistically not significant (p>0.05). Macroscopic examination of the organs of Group B and C revealed no abnormalities when compared with the organs of Group A (control). Histopathological analysis showed mild hepatocellular and renal toxicity in Groups B and C with extensive hemorrhages and periportal lymphocytic infiltrates.

PROBIOTIC AND β-LACTAM SENSITIVITY ASSESSMENT OF LACTIC ACID BACTERIA ISOLATED FROM TRADITIONALLY FERMENTED PRODUCTS OF MEGHALAYA

RAKESH GHOSH — 2024-12-01

Objective: The present study aimed to isolate, identify, and analyze the probiotic properties and β-lactam sensitivity in the Lactic Acid Bacteria (LAB) prevalent in Tungtap and Lung-seij, common traditionally fermented ethnic products throughout Meghalaya.

Methods: Bacterial pure colonies were identified using conventional biochemical tests and 16S rRNA Sanger sequencing. Slightly modified standard protocols were followed for the assessment of different probiotic properties.

Results: The selected LAB isolates were found Gram-positive, catalase, and oxidase-negative and exhibited resistance to most of the β-lactam antibiotics used in this study. No significant antibacterial activity was shown against tested strains. However, they showed strong bile salt and acid tolerance, as well as high auto aggregation and moderate hydrophobicity properties, which represent their probiotics properties. Extracellular Polymeric Substances (EPS) yield was highest for the TT2 isolate, while TT10 showed maximal siderophore production. Biofilm formation varied, with BS2 and BS5 showing strong adherence. Sequencing results confirm that the majority of the isolates belonged to the Lactiplantibacillus and Ligilactibacillus genera. Moreover, further genetic analysis confirmed the presence of β-lactamase genes in the selected isolates.

Conclusion: The presence of these genes suggests that the isolates may become reservoirs for Antimicrobial Resistance Genes (ARG) in traditional fermented foods. Further study is required to establish whether the isolates are transmitting their antimicrobial resistance genes during co-culture under different stress conditions and transportation.

ENHANCING FLUCONAZOLE SOLUBILITY AND BIOAVAILABILITY THROUGH SOLID DISPERSION TECHNIQUES: EVALUATION OF POLYETHYLENE GLYCOL 6000 AND SODIUM CARBOXYMETHYLCELLULOSE SYSTEMS USING FIBER OPTICS

WAFA SULAIMAN AL HATTALI — 2024-12-01

Objective: The triazole antifungal fluconazole is widely used for treating mycotic infections, but its efficacy is limited by its poor aqueous solubility and low dissolution rate, leading to reduced oral bioavailability. This study aimed to enhance the solubility and dissolution rate of fluconazole using solid dispersion techniques with Polyethylene Glycol 6000 (PEG 6000) and Sodium Carboxymethylcellulose (SCMC) as carriers.

Methods: Solid dispersions were prepared using the fusion method, and their physicochemical properties were evaluated against physical mixtures and pure drug samples.

Results: The solid dispersion showed a significant increase in the dissolution rate, achieving 89.01% drug release in 180 min compared to 40.3% for the pure drug (p<0.0032) and 84.1% for the physical mixture (p<0.0453). The encapsulation efficiency of the solid dispersion was 39.24%, with a drug loading capacity of 19.62%. Fourier Transform Infrared (FTIR) spectroscopy confirmed the stability of the drug within the dispersion, while Scanning Electron Microscopy (SEM) revealed amorphous particles, indicating enhanced solubility.

Conclusion: These results demonstrate that the solid dispersion of fluconazole with PEG 6000 and SCMC significantly improves its dissolution rate and flow properties, providing a promising strategy for enhancing the oral bioavailability of poorly water-soluble drugs.

TECHNICAL AND PATENT PERSPECTIVE ON FILM FORMING TOPICAL SPRAYS

M. H. DEHGHAN — 2024-12-01

Film-forming systems were a viable option for topical and transdermal medication administration in the present study. Medication administered via the skin serves two purposes: topical treatment of skin disorders and transdermal drug absorption into the circulation. Apart from the ease of self-administration, the topical route provides a broad and diverse surface and functions as a substitute for oral and hypodermic injection drug delivery routes. Existing dosage forms, such as creams, patches, and ointments, have several drawbacks. In addition to being unsightly, patches can be painful to put on curved surfaces, create discomfort while peeling off, and most often cause skin irritation because of their occlusive qualities, which block sweat ducts and prevent perspiration from evaporating from the skin surface. This review encompasses the mechanism of polymers, such as ethyl cellulose and Eudragit types, plasticizers, and penetration enhancers utilized in film formation. Overall, polymeric film-forming sprays exhibit substantial potential for the convenient administration of antibiotics and antiseptics to treat bacterial, fungal, and viral skin infections. The application of topical medication is thought to result in both local and systemic effects. The physicochemical characteristics of the medication and patient adherence determine how well the topical treatment works. Poor permeability and poor adherence to the skin are some of the disadvantages of conventional pharmaceutical formulations for topical and dermatological administration. The development of medication delivery technologies intended for topical administration to the skin includes the use of topical film-forming systems.