A New Stability-Indicating RP-HPLC Method for Simultaneous Quantification of Diacerein and Aceclofenac in Novel Nanoemulgel Formulation and Commercial Tablet Dosage Form in the Presence of their Major Degradation Products Using DoE Approach.

The present study aimed to develop a simple, robust, sensitive and effective stability-indicating reversed-phase high-performance liquid chromatography method for simultaneous quantification of diacerein (DCN) and aceclofenac (ACE) in novel nanoemulgel formulation and commercial tablets in the presence of their main degradation product: rhein (RH) and diclofenac sodium (DLS), respectively. A fractional factorial design was used to screen the crucial independent factors, whereas a central composite design was used for the optimization of the chromatographic conditions. The separation was carried out on Phenomenex C18 column (5 µm, 250 × 4.6 mm), using a mobile phase consisting of phosphate buffer pH 3 (0.1% v/v orthophosphoric acid) and acetonitrile (40:60 v/v) at a flow rate of 1 mL/min with detection at 264 nm. The analytes were exposed to a variety of stress conditions, including heat, alkali, acid, oxidation, photochemical, humidity and hydrolysis. DCN, ACE, RH and DLS were found to have retention times of 4.32 ± 0.15, 5.77 ± 0.07, 8.28 ± 0.20 and 9.10 ± 0.18 min, respectively. The percent recovery for all four analytes was found to be between 98 and 102, and the procedure was discovered to be linear in the range of 0.1-64 µg/mL with R2 value > 0.999. The established method was validated as per ICH guidelines and successfully used to assay DCN and ACE in their combined marketed tablet dosage form and developed nanoemulgel formulation.

Development and Validation of Novel RP-HPLC Method for the Simultaneous Estimation of Capecitabine and Thymoquinone in the Biodegradable Nanoparticles using Full Factorial Design.

An innovative RP-HPLC technique was devised to simultaneously quantify thymoquinone (TQ) and capecitabine (CAP) in newly designed polymeric nanoparticles. A unique chromatographic approach was created, optimized and validated using Design-Expert® (design of experiment) in compliance with ICH requirements. A 24 factorial design examined the influence of variables on method responses. The method found linear between 0.25 and 16 µg/mL, with an R2 value of 0.999. The detection and quantification limits for CAP were 0.05 and 0.16 µg/mL, respectively, and 0.12 and 0.38 µg/mL for TQ, respectively, and 97-100% recovery in plain drug solution and 100-102% in nanoformulation were achieved. A purposeful modification examined by analysis of variance revealed that the experimental model was significant (P = 0.0001). The total drug content in nanoformulation was 8.68 mg, and the entrapment efficiency was 84.79%. Based on the findings, it is possible to infer that the use of the Quality by Design methodology resulted in the development of a more accurate technique capable of producing consistent, dependable, high-quality data and precise in quantifying CAP and TQ in bulk and nanoparticulate systems.

Current Novel Drug Deliveries for Oral Cancer: A Chronotherapeutic Approach.

Oral squamous cell carcinoma is a malignant disease that is causing considerable mortality worldwide. Conventional treatment approaches, like surgery, cause destructive alterations in facial appearance and oral function impairments associated with psychological and social functioning. Chemotherapy exhibits low bioaccessibility of the anticancer drugs, multiple drug resistance, higher dose necessities, which elevate toxicities to the normal cells, low therapeutic index, and non-specific targeting. Radiation therapies significantly affect the well-being of the patient and impair the quality of life. Therefore, chemotherapeutics are developed that can either actively or passively target the carcinomas, reduce the adverse side effect, and improve therapeutic efficacy. Innovations in novel drug delivery systems deliver the drugs to the desired site of action with better treatment approaches with reduced toxicities to the normal cells and improve the health and survival rate of the patient. Cancer chronotherapy enhances the treatment proficiency by administration of the drugs at the best time, considering biological timings to improve the treatment profiles. Chronotherapy provides benefits to the current anticancer therapies, with minimum adverse effects to the healthy cells. This review discusses the risk factors for oral carcinomas, targeted therapy by nanocarriers, nanotechnology approaches, the role of circadian rhythm in the management of oral cancer, and advances in controlled drug delivery.

Exploring the Solvent-Anti-solvent Method of Nanosuspension for Enhanced Oral Bioavailability of Lovastatin

Objectives: Lovastatin is an antilipidemic drug that belongs to the class of statins that has poor oral bioavailability due to its low solubility and variable dissolution rate. The main aim of this study was to enhance the solubility and dissolution rate of the drug and understand its oral bioavailability. Materials and Methods: Lovastatin nanosuspension was formulated using a solventanti-solvent method using a probe sonication technique. A nanosuspension was prepared, using hydroxypropyl methylcellulose (HPMC) K15M and pluronic F68 as stabilizers. The formulated nanosuspensions were characterized for particle size, polydispersity index (PDI) zeta potential, surface morphology, and in vitro release rate. Further, an in vivo bioavailability study and stability studies were also performed. Results: Optimized formulation showed a particle size of 127±0.01 nm, a PDI of 0.492±0.001, and a zeta potential of -37.9 mV, which indicates good stability. Morphological study showed that the particles were in the nano range. The drug content was found to be in the range of 73-87%. In vitro release revealed much faster release of the drug in one hour compared to the pure drug and its marketed formulation. In vivo bioavailability study was carried out in Wistar rats, which showed improvement in bioavailability by approximately 2.5 folds compared with the marketed formulation. Stability studies indicated that the optimized formulation F2 was more stable at 4°C±2°C. Conclusion: The prepared lovastatin nanosuspension showed improvement in solubility, dissolution rate, and oral bioavailability compared to the pure drug and its marketed formulation. Hence, lovastatin nanosuspension may be a potentially valuable tool for improving the oral bioavailability of lovastatin.

Development of hollow/porous floating beads of metoprolol for pulsatile drug delivery.

The purpose of this work was to develop hollow calcium pectinate beads for floating pulsatile release of metoprolol tartrate intended for chronopharmacotherapy. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, hollow/porous beads were prepared by simple process of acid-base reaction during ionotropic cross-linking using low methoxy pectin, xanthan gum, sodium carboxy methyl cellulose, guar gum, locust bean, gellan gum and calcium chloride as a cross-linking agent. Based on the preliminary studies optimized polymers were selected for formulation design with different polymers ratio concentrations. The obtained floating beads were studied for entrapment efficiency, buoyancy study, swelling index, surface morphology, in vitro release, stability studies and in vivo floating study. The floating beads obtained were porous, float up to 12-24 h. The radiological studies (X-rays) pointed out the capability of the system to release drug in lower parts of GIT after a programmed lag time for hypertension. The floating beads provided expected two-phase release pattern with initial lag time during floating in acidic medium followed by rapid pulse release in phosphate buffer. From the accelerated stability studies, it was observed that the formulations are quite stable. All formulations followed first-order release kinetics by diffusion mechanism. This approach suggested the use of hollow calcium pectinate microparticles as promising floating pulsatile drug delivery system for site- and time-specific release of drugs acting as per chronotherapy of diseases.

Development and characterization of chronomodulated drug delivery system of captopril.

BACKGROUND: Hypertension shows circadian rhythm that there is a rise in pressure from the time of waking or before (about 4 to 8 a.m.), in most people. Conventional drug delivery system of captopril is inappropriate for the delivery of drug, as they cannot be administered just before the symptoms are worsened, because during this time the patients are asleep, bedtime dosing of captopril will not provide a therapeutic plasma drug concentration at the early hours of morning because of poor pharmacokinetic profile and shorter half-life of 1.9 hours. Thus, this study attempts to design and evaluate a chronomodulated pulsatile drug delivery system of captopril which was aimed to release the drug after a lag time of 6 hours. MATERIALS AND METHODS: Present delivery system was prepared by rupturable coating method. The core containing captopril as a bioactive compound were prepared by direct compression method and then coated sequentially with an inner swelling layer containing hydrocolloid HPMC E5 and an outer rupturable layer consisted of Eudragit RL/RS (1 : 1). Total 12 formulations with different levels of inner swelling layer and outer polymeric layer were prepared and subjected to various processing and formulative parameters like the effect of core composition, level of swelling layer, and rupturable coating on lag time was investigated. In vitro drug release and rupture tests were performed using United States Pharmacopoeia paddle method at 50 rpm in 0.1N HCl and phosphate buffer of pH 6.8. RESULTS: The results showed that as the amount of inner swelling layer increases, the lag time decreases and as the Eudragit coating level increases, the lag time increases and percent water uptake of time-dependent pulsatile release system decreases. The presence of an osmotic agent and effervescent agent helped in shortening of lag time. CONCLUSION: The system was found to be satisfactory in terms of release of the drug after the lag time of 6 hours.