Tolfenamic acid (TA) is a fenamate nonsteroidal anti-inflammatory drug with expanding therapeutic potential, but its clinical use is limited by systemic side effects and the lack of topical formulations. Developing a stable topical gel may enable localized delivery of TA while minimizing systemic exposure. In the present study, simple hydroalcoholic gel formulations of TA with carboxymethylcellulose sodium (CMC) were prepared, with or without propylene glycol (PG), at pH 6.5. Before the formulation step, the interactions and compatibility of the TA/CMC (1:1) physical mixtures were studied using Fourier transform infrared spectroscopy and high-performance liquid chromatography. The formulated gels were stored at room temperature (27 ± 2°C) for six months and evaluated for their physical and chemical stability. The results indicated that gels prepared without PG showed greater moisture evaporation, resulting in higher viscosity, spreadability, and swelling index, with lower weight loss. No syneresis was observed in either gel formulation under different conditions, except under acidic conditions, where syneresis was observed. Microscopic evaluation of the formulations revealed polymorphic changes of the drug in the gels during storage. Both gels demonstrated optimal chemical stability, with negligible degradation throughout the study. Release kinetic studies indicated that TA followed the Higuchi model, with almost 100% drug release within 2.5 h.

The present work investigates the thermal stability and degradation kinetics of TA in aqueous–ethanolic mixtures (50–100

This review explores the innovative approaches in localized drug delivery systems specifically designed to manage periodontal diseases (PD). The primary focus is on how these systems enhance the concentration of therapeutic agents at the site of infection, thereby minimizing systemic side effects and improving treatment outcomes. It emphasizes the role of biodegradable and bioadhesive polymers as carriers for sustained drug release. The chapter reviews different local drug delivery systems, such as fibers, films, chips, microparticles, and gels, highlighting their mechanisms of action, advantages, and limitations. It also discusses commonly used drugs, including chlorhexidine, doxycycline, metronidazole, and tetracycline, which are encapsulated within these systems to improve therapeutic efficacy. Additionally, the chapter delves into the polymers used in drug delivery, categorizing them into natural and synthetic biodegradable polymers, each offering unique benefits regarding biocompatibility and drug release kinetics. Polymeric therapeutics for controlled and sustained release further support the development of localized treatments. Overall, this chapter underscores the advancements in drug delivery technologies that promise to revolutionize the treatment of PD by reducing systemic side effects and optimizing therapeutic outcomes.

Ciprofloxacin hydrochloride (CH) is a widely used fluoroquinolone antibiotic. Accurate, cost-effective methods are essential for its routine quality control. This study aimed to develop and validate simple UV spectrophotometric and spectrofluorimetric methods for quantifying CH in bulk and pharmaceutical formulations. UV analysis was performed at 271 nm, while fluorescence measurements were taken at 335 nm (excitation) and 416 nm (emission) in phosphate buffer (pH 7). Validation was conducted in accordance with the International Council for Harmonisation (ICH) guidelines for linearity, accuracy, precision, Limit of Detection (LOD), Limit of Quantification (LOQ), robustness, and solution stability. Results were compared with an official HPLC method. Both methods demonstrated excellent linearity in the range of 0.4-2.0 × 10⁻⁵ M (r² = 0.9999). The limits of detection (LOD) and quantification (LOQ) were 0.64/1.95 × 10⁻⁶ M for the UV method and 0.66/1.99 × 10⁻⁶ M for the fluorescence method. Recovery values ranged from 99.27% to 99.92% (UV) and 98.60% to 100.32% (fluorescence), with %RSD values below 2%, indicating good precision. Robustness testing revealed minimal effects from deliberate variations in experimental conditions, and the results showed strong agreement with the compendial HPLC method UV spectrophotometric and spectrofluorimetric methods proved to be accurate, sensitive, and reproducible. The UV method is ideal for basic lab setups, while fluorescence offers greater sensitivity for lower concentrations. Comparable results with HPLC confirm their suitability. Validated UV and fluorescence methods provide efficient, accurate, and lowcost alternatives to HPLC for quality control of CH in pharmaceutical analysis.

Doxycycline hyclate (DH) is an antibiotic from the tetracycline family used to treat gram-positive and gram-negative bacterial infections. The present study aims to develop and validate a green ultra-high-performance liquid chromatographic (UHPLC) method using the analytical quality by design (AQbD) approach. This method has been validated following the ICH guidelines. The mobile phase used to estimate DH is a mixture of acetonitrile and KCl - HCl buffer (70:30, v/v, pH 2.0), which is run on a C18 column at a flow rate of 0.1 ml/min. at a detection wavelength of 350 nm. The proposed UHPLC method is found to be linear in the concentration range of 0.50-1.10 mg%, with a correlation coefficient of 0.9999. It has shown high accuracy (97.69-101.56%) and precision (RSD 0.63-0.95%). The method is also suitable for analyzing DH in pharmaceutical dosage forms (tablets, capsules) and biological samples (blood, saliva). A statistical comparison with the official USP HPLC method showed no significant mean difference (t-test). In contrast, a significant difference has been noted between the variances (F-test). The four green assessment tools (NEMI, Analytical Eco Scale, GAPI, and AGREE) have been used to evaluate the proposed method's greenness and environmental safety, revealing that it is a relatively green, economical, time-saving, and energy-efficient process.

Chlorhexidine (CHX) is a synthetic cationic biguanide commonly used in dentistry to control infections. In the present study, cost-effective biodegradable dental chips of CHX (0.2%) with varying concentrations of high-molecular-weight chitosan (2%, 3%, and 4%) were prepared using the solvent casting method. The identification, purity, and interaction between the active drug and excipients have been confirmed using FTIR spectrometry. The formulated chips exhibited a pH of around 5, with excellent folding endurance of >= 1000, a thickness of 0.34-0.42 mm, and a moisture loss of about 10-14%. Organoleptically, the chips were consistent for at least three months at room temperature. The assay of CHX was performed using a validated HPLC method. The content uniformity of the chips was found to be greater than 90%, indicating a uniform distribution of the active drug. The release of CHX from the chips slowed down from 31 to 72 h with an increase in polymer concentration from 2 to 4%. The release followed the Higuchi model for 2% and 3% chips and the Korsmeyer-Peppas model for 4% chips. All the chips demonstrated stability for only one month under accelerated temperature and humidity conditions (i.e., 40 degrees C/75% RH). Significant antimicrobial activity has been observed for both placebo and CHX-loaded chips against various standard and clinical isolates, with good activity on cementum. The formulated CHX dental chips offer an economical and effective drug delivery system for treating periodontal infections, due to their potent antimicrobial effect and sustained drug release, which facilitates the desired therapeutic effects.

OBJECTIVES:The primary aim of this study was to develop an effective treatment strategy for periodontal diseases that maximizes therapeutic effects while minimizing systemic adverse effects. Specifically, the study focused on creating a xerogel-based localized drug delivery system for the slow release of doxycycline hyclate (DH) to treat periodontal disease. METHODS:Xerogels were prepared using the solvent casting method, with the solvent being evaporated slowly at ambient conditions. The prepared DH xerogels underwent comprehensive characterization to assess their in-silico compatibility, pharmacokinetics, and physicochemical properties. The properties studied included drying time and rate, thickness, moisture content, swelling index, organoleptic properties, scanning electron microscopy, FTIR spectroscopy, differential scanning calorimetry, drug release and kinetics, and antibacterial activity. RESULTS:In-silico studies demonstrated compatibility between the ingredients, indicating minimal adverse effects on the body. The analysis revealed hydrogen bonding between the drug and polymers, changing the drug's crystallization characteristics to an amorphous form. The release profiles of DH from the xerogels indicated a slow release, ranging from 29.42% to 66.30% over 10 hours, following the Hopfenberg model. CONCLUSION:The findings of this study suggest that the formulated xerogels are well-suited for periodontal applications. The slow-release profile of DH from the xerogels offers a promising approach for localized treatment of periodontal disease, reducing the risk of systemic adverse effects. This data is valuable for dental practitioners and pharmaceutical formulators, providing a new avenue for enhancing periodontal disease treatment.

It is essential to adopt effective therapy strategies for periodontal diseases to achieve optimal results while avoiding adverse effects on the system. This study has developed various PEGylated chitosan-based biodegradable xerogels for localized release of doxycycline hyclate (DH) to treat periodontal infectious diseases. The xerogels were formulated using the solvent casting method, and the solvent (0.25 M HCl) was slowly evaporated at ambient conditions. Two different molecular weights were employed for chitosan and polyethylene glycol, and twelve combinations, including the placebos and controls, were prepared for the formulation of xerogels. Different physical and chemical characteristics of the prepared DH xerogels were studied, such as drying time and rate, thickness, moisture content, swelling index, organoleptic characteristics, scanning electron microscopy, FTIR spectrometry, differential scanning calorimetry, drug release and kinetics, and antibacterial activity. The results revealed that the drug transforms from a crystalline to an amorphous state, thus rapidly releasing the drug (> 60% in 30 min. in all xerogels), followed by a sustained release up to 10 h. The release kinetics results revealed that the drug followed the Korsmeyer-Peppas model. It is concluded that the formulated DH-loaded xerogels showed promising results for use in the periodontal pockets to treat various infectious diseases.

Donepezil (DPZ) photosensitized degradation by riboflavin (RF) at pH 2.0-12.0 has been carried out in aerobic and anaerobic conditions under UV and visible irradiation to give an idea to pharmaceutical formulators to develop a stable co-formulation to administer to elderly patients with neurodegenerative diseases (Alzheimer's disease, Parkinson's disease). The photolysis rate constants (k obs) in aerobic and anaerobic conditions in the presence of RF (0.1-0.5 × 10-4 M) range from 0.25-11.5 and 0.025-1.120 × 10-2 min-1, respectively. RF catalyzes the photodegradation of DPZ, and the second-order (k 2) constants in aerobic and anaerobic conditions range from 0.32 to 8.22 and 0.032 to 0.805 × 10-2 M-1 min-1, respectively, indicating that with an increase in the concentrations of RF, the rate of photolysis of DPZ also increases. The k-pH profile shows a bell-shaped curve from pH 2.0 to 4.0 and from pH 5.0 to 12.0, forming a sigmoid curve. The two-component spectrometric and HPLC green methods have been developed and validated for estimating DPZ and RF in pure and degraded solutions. Additionally, computational studies have been conducted to assess the formation of the ground-state complex, binding affinity, and molecular interactions between DPZ and RF.

The photostabilization of 5-fluorouracil (5-FU) has been carried out in the pH range of 2.0-12.0 using cyclodextrins (α-, β-, γ-) as a complexing agent. The inclusion complex formation between 5-FU and CDs has been evaluated using conductometry, FTIR spectroscopy, NMR spectroscopy, differential scanning calorimetry (DSC), and molecular docking simulations. The loss of absorbance at 266 nm for 5-FU in the presence of CDs indicates its photodegradation. The entrapment of 5-FU in α-, β-, and γ-CDs ranges from 22.0-58.0, 30.0-64.0, and 42.0-77.0%, respectively, indicating the formation of inclusion complexes of CDs with 5-FU. The values of Stern-Volmer fluorescence quenching constants and binding constants for α-, β- and γ-CDs are 1.10, 1.69, 3.06 × 103 L mol-1 and 2.89, 3.11, 3.62 103 L mol-1, respectively. The apparent first-order rate constants (k obs) for the photodegradation of 5-FU in the presence of α-, β-, and γ-CDs are 1.75-5.12, 1.21-4.89, and 0.85-4.69 × 103, min-1, respectively. The photochemical interaction (k 2) of 5-FU with α-, β-, and γ-CDs ranges from 0.25-0.49, 0.63-1.47, and 0.79-2.14 M-1 min-1 in the pH range 2.0-12.0. The mode of photochemical interaction of 5-FU and CDs and the photostabilization of 5-FU is described based on H-atom abstraction by 5-FU from CD and radical-radical recombination. The computational analysis complemented the experimental findings, showing a significant second-order donor-acceptor interaction, particularly LP → π*, between the hydroxyl groups of γ-CD and the carbonyl groups of 5-FU. The natural population analysis further revealed a shift in electron density from γ-CD to 5-FU, indicating a protective charge-transfer mechanism that contributes to the photostabilization of 5-FU.

Donepezil HCl (DH) is commonly used for the treatment of different neurological disorders such as dementia, Alzheimer’s, and Parkinson’s diseases. So far, there is no stability-indicating spectrofluorimetric assay method for the estimation of DH that has been reported. Therefore, this study aims to develop and validate a green and eco-friendly stability-indicating spectrofluorimetric assay method for the estimation of DH in pure, dosage form, and degraded solutions. The green and eco-friendly spectrofluorimetric method was developed and validated by the International Council on Harmonization guidelines, and the parameters mentioned in the guidelines were studied. The maximum pH for the fluorescence intensity of DH has been studied in the pH range 1.0–14.0, and found that from pH 1.0 to 8.0, there is no considerable difference in the fluorescence intensity of DH. Therefore, pH 7.0 was selected for the assay of DH, and the pKa value was determined as 8.20. The calibration curve for DH is linear in the 0.50–3.50 × 10–5 M concentration range. The accuracy and precision of the method are in the range of 100.07–100.70

Collagenases are enzymes that break down collagen and are used in wound healing and treating various disorders. Currently, collagenase is commercially available in only ointment and injectable forms and is sensitive to various environmental factors. In the present study, different hydrogel formulations of collagenase have been prepared at pH 6.5 using carboxymethylcellulose sodium and zinc acetate with and without humectants such as propylene glycol (PG) and glycerin (GL) in varying concentrations. The formulated gels were stored at room temperature (25±2°C, 60±5% RH) and refrigerator temperature (5±3°C) for six months to evaluate their physical and up to six years for chemical stability. The gels were subjected to various tests, including organoleptic studies, spreadability, moisture content, swelling index, swelling/de-swelling, syneresis, viscosity, gelation time, and weight variation. The purity and molecular weight of collagenase have been determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). At the same time, its activity during the storage period was evaluated by gelatin zymography. Casein zymography was also performed to detect any caseinase contamination in the formulations. The release of the enzyme from different gel formulations was assessed using the Franz diffusion apparatus and analyzed by gelatin zymography. The results showed some physical changes that were more prominent in gels stored at room temperature than those kept refrigerated. The difference in humectant concentration was also found to affect the stability of gels. PG was found to be a better humectant than GL, particularly in a concentration of 25%. The zymography results indicated that collagenase was stable in all formulations kept in the refrigerator. In contrast, its complete degradation was noted in the preparations stored at room temperature within a month. The data generated in this study will help the formulators to commercialize a relatively economical gel formulation of collagenase that is highly stable for up to six years at refrigerator temperature (5±3°C).

Vortioxetine (VX) is a multimodal novel antidepressant drug that belongs to the class of serotonin modulators and simulators (SMS). It is widely used for the treatment of major depressive disorder (MDD). VX possesses a multimodal mechanism of action that includes inhibition of serotonin transporter (SERT) and direct modulation of serotonin receptors (i.e., 5-HT1A, 5-HT1B, 5-HT3, 5-HT1D, and 5-HT7). This monograph presents a comprehensive review that includes a description (i.e., taxonomy, nomenclature, impurities, etc.), different synthesis methods, physical characteristics (i.e., appearance, color, solubility, thermodynamic properties, etc.), methods of analysis (i.e., spectroscopic, chromatographic, electrochemical methods), stability and degradation, pharmacology (i.e., pharmacodynamics, pharmacokinetics), therapeutic uses, and adverse and toxic effects of VX.

Fenamates are the most crucial non-steroidal anti-inflammatory drugs (NSAIDs) used to treat pain-related diseases. The clinically prescribed drugs of the fenamate group include mefenamic acid, tolfenamic acid, meclofenamic acid, flufenamic acid, and niflumic acid. Due to their widespread use, all these drugs are considered as the most common water and sewerage pollutants. Studies have been performed to remove these contaminants from water sources by various forced degradation procedures, but the number of studies in this area is limited. In this chapter, an effort has been made to review the degradation of multiple fenamates in different systems and the factors affecting the degradation rates with the proposed degradation pathways.

BACKGROUND:Tolfenamic acid (TA) belongs to the fenamates class of nonsteroidal anti-inflammatory drugs. Insufficient information is available regarding the availability of a reliable and validated stability-indicating method for the assay of TA.OBJECTIVE:A relatively simple, rapid, accurate, precise, economical, robust, and stabilityindicating RP-HPLC method has been developed to determine TA in pure and tablet dosage forms.METHODS:The method was validated according to the ICH guideline, and parameters like linearity, range, selectivity, accuracy, precision, robustness, specificity, and solution stability were determined. TLC and FTIR spectrometry were used to ascertain the purity of TA. The specificity was determined with known impurities and after performing forced degradation, while the robustness was established by Plackett-Burman's experimental design. The mobile phase used for the analysis was acetonitrile and water (90:10, v/v) at pH 2.5. The detection of the active drug was made at 280 nm using a C18 column (tR = 4.3 min.). The method's applicability was also checked for the yellow polymorphic form of TA.RESULTS:The results indicated that the method is highly accurate (99.39-100.80%), precise (<1.5% RSD), robust (<2% RSD), and statistically comparable to the British Pharmacopoeia method with better sensitivity and specificity.CONCLUSION:It was observed that the stress degradation studies do not affect the method's accuracy and specificity. Hence the proposed method can be used to assay TA and its tablet dosage form.

Ascorbic acid (AH2) photoxidation sensitized by riboflavin (RF) has been studied between pH 2.0 and 12.0 in ambient air and anaerobic environment using UV and visible irradiation sources. The kinetics of AH2 degradation in aqueous medium along with RF is found to be first-order for its photodegradation. AH2 photolysis rate constants in aerobic and anaerobic conditions with RF (1.0-5.0 x 10-5 M) are 0.14-3.89 x 10-2 and 0.026-0.740 x 10-2 min-1, respectively. The rate constants (k2) of second-order kinetics for AH2 and RF photochemical interaction in aerobic and anaerobic conditions are in the range of 0.24-3.70 to 0.05-0.70 x 10-3 M-1 min-1, respectively, which manifests that increasing the RF concentration also increases the rate of photodegradation (photooxidation) of AH2. The k2 versus pH graph is bell-shaped which indicates that increasing the pH increases photolytic degradation rate of AH2 with RF. Increasing the pH results in the increased ionization of AH2 (ascorbyl anion, AH-) and redox potential which leads to the higher rates of photodegradation of AH2. Two-component spectrophotometric (243 and 266 nm, AH2 and RF, respectively) and high-performance liquid chromatography (HPLC) methods have been used to determine the concentration of AH2 and RF in pure and degraded solutions. The results obtained from these two methods are compared using a student t-test which showed no noteworthy difference between them.

The photolysis of tolfenamic acid (TA) in aqueous and organic solvents formed 17 photoproducts, of which 9 were reported for the first time.

This chapter presents an overall account of cyclodextrins (CDs) with a brief description of the history, classification, and properties of these macromolecules. CDs act as complexing agents for drugs to form CD-drug inclusion complexes by various techniques. These complexes lead to the modification of the physicochemical properties of drugs to make them more soluble, chemically, and photochemically stable, and less toxic. It focuses in detail on various pharmaceutical uses of CDs and their derived forms in drug solubility, bioavailability, drug stability, drug delivery, and drug safety which have been specifically highlighted. The role of CDs and derivatives as excipients in the drug formulation of solid dosage forms, parenteral dosage forms, and anticancer drugs has been emphasized. Some other applications of CDs in cosmetics, environmental protection, food technology, and analytical methods have been described.