Higuchi Equation Research Articles

Fu'cupping Physical Permeation-Enhancing Technique Enhances the Therapeutic Efficacy of Corydalis yanhusuo Gel Plaster.

Corydalis yanhusuo, a traditional Chinese medicine, is widely used to treat various pains, and its active ingredients are alkaloids. This study aimed to develop a new type of transdermal gel plaster containing the extract of C. yanhusuo. Studies have shown that Fu'cupping physical permeation-enhancing technique can promote the penetration of alkaloids and improve the efficacy of drugs. A transdermal gel plaster containing the extract of C. yanhusuo was prepared and optimized using an orthogonal experimental design. The skin permeation ability of the gel plaster was studied in vitro, while the anti-inflammatory and analgesic effects of the prepared patch alone or with Fu'cupping physical permeation-enhancing technique were evaluated in a rat model. The formulation of a gel plaster containing C. yanhusuo extract was successfully prepared with an optimized composition consisting of glycerin (15 g), sodium polyacrylate (2 g), silicon dioxide (0.3 g), ethanol (2 g), aluminum oxide (0.1 g), citric acid (0.05 g), the C. yanhusuo extract (3 g), and water (15 g). The cumulative transdermal permeation of dehydrocorydaline, corypalmine, tetrahydropalmatine, and corydaline in 24 h was estimated to be 569.7 ± 63.2, 74.5 ± 13.7, 82.4 ± 17.2, and 38.9 ± 8.1 µg/cm2, respectively. The in vitro diffusion of dehydrocorydaline and corydaline followed the zero-order kinetics profile, while that of corypalmine and tetrahydropalmatine followed a Higuchi equation. The prepared gel plaster significantly reduced paw swelling, downregulated inflammatory cytokines, and mitigated pain induced by mechanical or chemical stimuli. The Fu'cupping physical permeation-enhancing technique further improved the anti-inflammatory and analgesic effects of the patch. The combined application of the Fu'cupping physical permeation-enhancing technique and the alkaloid gel plaster may be effective against inflammation and pain.

Formulation, design, and evaluation of valsartan sodium-sustained-release matrix tablets

The main aim of present work was to formulate and evaluate sustain release matrix tablets of Valsartan, an angiotensin II Receptor type 1 antagonist. Sustain release formulation are those which delivers the drug locally or systemically at a predetermined rate for a fixed period of time. The matrix tablet was prepared by direct compression method using by various concentration of chitosan and sodium alginate with combination of various release retardant polymer. The powder mixtures were subjected to various pre-compression parameters such as angle of repose, bulk density, tapped density and Carr’s index shows satisfactory result and the compressed tablets are evaluated for post-compression parameters such as weight variation, thickness, hardness, friability, drug content, in-vitro dissolution and stability studies. In-vitro dissolution studies were carried out for 24 hours using 0.1N HCl for first 2 hours and pH 6.8 phosphate buffers for 24 hours and the result showed that formulations F4 and F7 showed good dissolution profile to control the drug release respectively. Formulation containing higher concentration of chitosan and sodium alginate along with polymers sustainedthedrugreleasefor theperiodof24hours.The compatibilityof thedrug, polymers and other excipients were determined by FT-IR Spectroscopy. Results showed that the drug was compatible with polymers and other excipients. The release data was fitted to various mathematical models such as Zero-order, First-order, Higuchi equation and Korsmeyer- Peppas model to evaluate the kinetics and the drug release. The drug release followed first order and the mechanism was found to be non-Fickian. The stability studies were carried out for 3 months and result indicates that the selected formulations (F4and F7) were stable.

Transdermal diffusion research on functional substances of Jingu Zhitong Gel

This study systematically explored the transdermal diffusion law of functional substances of Jingu Zhitong Gel(JGZTG). The transdermal diffusion research methods of JGZTG were investigated by single factor trial with the automated transdermal(dry-heat) sampling system. High performance liquid chromatography(HPLC) content determination method was established to determine the contents of ferulic acid, senkyunolide I, cinnamic acid, hydroxy-ε-xanthoxylin, hydroxy-α-xanthoxylin, and hydroxy-β-xanthoxylin in the transdermal diffusion solution of JGZTG. The transdermal diffusion law of the components within 16 h was investigated. The results showed that the optimal transdermal diffusion method of JGZTG was as follows: Rat skin was used as the transdermal barrier; normal saline was used as the receiving medium; the dosage of JGZTG was 0.3 g, and the receiving solution was extracted by ethyl acetate. The results of transdermal diffusion showed that the release of ferulic acid, cinnamic acid, and senkyunolide I increased significantly at 0-8 h and slowed down at 8-16 h. The drug release was a synergic process of diffusion and dissolution, in which ferulic acid and cinnamic acid followed Higuchi and Ritger-Peppas equations, and liguolactone I followed Higuchi equation. The transdermal diffusion curves of hydroxy-ε-zanthoxylin, hydroxy-α-zanthoxylin, and hydroxy-β-zanthoxylin showed continuous release within 16 h, and the drug release was skeleton dissolution. The diffusion law followed zero-order equation, first-order equation, and Ritger-Peppas equation. In clonclusion, it is a controlled release of ferulic acid, ligustrone I, cinnamic acid, hydroxy-ε-pyrroxylin, hydroxy-α-pyrroxylin, and hydroxy-β-pyrroxylin in JGZTG, which can maintain stable blood drug concentration with 16 h, and the cumulative transmittance of each component with 12 h can reach 80% of cumulative transmittance with 24 h, which is in line with the clinical drug use law of bis in die.

Clinical Investigation of Valsartan Sustained-Release Matrix Tablets: Formulation Design and Performance Evaluation

The primary objective of this main study is to develop and assess the sustained-release matrix tablets containing Valsartan, an angiotensin II receptor type 1 antagonist. The powder mixtures underwent a thorough examination of pre-compression parameters and observed angle of repose, bulk density, tapped density, and Carr’s index, all of which exhibited satisfactory results. Following compression, the tablets were subjected to post-compression evaluations, including weight variation, thickness, hardness, friability, drug content, in-vitro dissolution, and stability studies. In-vitro dissolution investigations are conducted over 24 hours, employing 0.1 N HCL for the initial 2 hours and pH 6.8 phosphate buffer for the subsequent 24 hours. Notably, formulations F4 and F7 demonstrated promising dissolution profiles, effectively controlling the release of the drug. These formulations, enriched with higher concentrations of chitosan and sodium alginate in addition to other polymers, successfully sustained the drug release for the entire 24-hour duration. The compatibility of the drug, polymers, and other excipients was meticulously assessed using FT-IR Spectroscopy, affirming the harmonious interaction among these components. Further analysis involved fitting the release data to various mathematical models, including Zero-order, First-order, Higuchi equation, and Korsmeyer-Peppas model, to ascertain the kinetics and mechanisms governing drug release. Results indicated that the drug release adhered to first-order kinetics, with a non-Fickian mechanism prevailing. Stability studies conducted for 3 months provided reassurance regarding the stability of the selected formulations (F4 and F7), bolstering confidence in their potential for sustained release of Valsartan.

Norcantharidin-Encapsulated C60-Modified Nanomicelles: A Potential Approach to Mitigate Cytotoxicity in Renal Cells and Simultaneously Enhance Anti-Tumor Activity in Hepatocellular Carcinoma Cells.

The objective of this study was to examine the preparation process of DSPE-PEG-C60/NCTD micelles and assess the impact of fullerenol (C60)-modified micelles on the nephrotoxicity and antitumor activity of NCTD. The micelles containing NCTD were prepared using the ultrasonic method and subsequently optimized and characterized. The cytotoxicity of micelles loaded with NCTD was assessed using the CCK-8 method on human hepatoma cell lines HepG2 and BEL-7402, as well as normal cell lines HK-2 and L02. Acridine orange/ethidium bromide (AO/EB) double staining and flow cytometry were employed to assess the impact of NCTD-loaded micelles on the apoptosis of the HK-2 cells and the HepG2 cells. Additionally, JC-1 fluorescence was utilized to quantify the alterations in mitochondrial membrane potential. The generation of reactive oxygen species (ROS) following micelle treatment was determined through 2',7'-dichlorofluorescein diacetate (DCFDA) staining. The particle size distribution of the DSPE-PEG-C60/NCTD micelles was determined to be 91.57 nm (PDI = 0.231). The zeta potential of the micelles was found to be -13.8 mV. The encapsulation efficiency was measured to be 91.9%. The in vitro release behavior of the micelles followed the Higuchi equation. Cellular experiments demonstrated a notable decrease in the toxicity of the C60-modified micelles against the HK-2 cells, accompanied by an augmented inhibitory effect on cancer cells. Compared to the free NCTD group, the DSPE-PEG-C60 micelles exhibited a decreased apoptosis rate (12%) for the HK-2 cell line, lower than the apoptosis rate observed in the NCTD group (36%) at an NCTD concentration of 75 μM. The rate of apoptosis in the HepG2 cells exhibited a significant increase (49%), surpassing the apoptosis rate observed in the NCTD group (24%) at a concentration of 150 μM NCTD. The HK-2 cells exhibited a reduction in intracellular ROS and an increase in mitochondrial membrane potential (ΔψM) upon exposure to C60-modified micelles compared to the NCTD group. The DSPE-PEG-C60/NCTD micelles, as prepared in this study, demonstrated the ability to decrease cytotoxicity and ROS levels in normal renal cells (HK-2) in vitro. Additionally, these micelles showed an enhanced antitumor activity against human hepatocellular carcinoma cells (HepG2, BEL-7402).

Formulation and in vitro Evaluation of Verapamil Hydrochloride Floating Tablets

The present research work aims to formulate and evaluate novel sustained-discharge floating tablets of verapamilhydrochloride (VPH) which is used for the treatment of hypertension. We aim to use a direct compression technique to formulatethe floating tablets. The characterization of the formulation of VPH was carried out by employing FT-IR and DSC studies, whichshowed that there was no chemical interaction between the drug and polymers, such as HPMC K100M, chitosan, and sodiumalginate. The tablets are designed to have good in-vitro buoyancy, and they remain afloat in the dissolution medium. The bestformulation (F7) is chosen based on its maximum drug discharge (91.91±2.25%) and drug content (97.20±2.71%) over 12h. Thedischarge kinetics of the drug from the tablets are analyzed using various mathematical models, such as zero order, first order,Higuchi, and Korsmeyer's equations. These models help explain and predict drug discharge behavior over time. The studyconcludes that a proper balance between the sustained-release polymer and the gas-forming agent is essential for efficient in-vitrobuoyancy and sustained drug discharge. Formulation F7, which utilized sodium alginate, appears to be the most promising in termsof drug discharge and content.

Facile Synthesis of Three Types of Mesoporous Silica Microspheres as Drug Delivery Carriers and their Sustained-Release Properties.

Mesoporous silica nanoparticles (MSNs) are one of the most promising carriers for drug delivery. MSNs have been widely used in pharmaceutical research as drug carriers because of their large pore volume, high surface area, excellent biocompatibility, nontoxicity, ease to functionalize, and sustained release effects. MSNs have attracted much attention during drug delivery because of their special structure. The present study aimed to synthesize mesoporous silica nanoparticles (MSNs), dendritic mesoporous silica nanoparticles (DMSN), and hollow mesoporous silica nanoparticles (HMSN) through facile methods, and to compare the drug release properties of nano-porous silica with different pore structures as a stroma for PUE drug. MSN, DMSN, and HMSN were characterized by SEM, TEM, FT-IR, nitrogen adsorptiondesorption isotherms, XRD, and zeta potential methods. Subsequently, puerarin (PUE) was used as the active ingredient and loaded into the three mesoporous materials, respectively. And, the drug delivery behavior was measured in PBS solution with different pH values. The sustained-release properties of MSN, DMSN, and HMSN loaded with PUE were investigated. Finally, the biocompatibility and stability of MSN, DMSN, and HMSN were studied by MTT assay and hemolysis assay. Our results showed that MSN, DMSN, and HMSN were successfully synthesized and the three types of mesoporous silica nanoparticles had higher drug loading and encapsulation efficiency. According to the first-order release equation curve and Higuchi equation parameters, the results showed that the PUE-loaded MSN, DMSN, and HMSN exhibited sustained-release properties. Finally, MTT and hemolysis methods displayed that MSN, DMSN, and HMSN had good biocompatibility and stability. In this study, MSN, DMSN, and HMSN were successfully synthesized, and to compare the drug release properties of nano-porous silica with different pore structures as a stroma for PUE drug, we provided a theoretical and practical basis for the application of PUE.

The Preparation and In-vitro Evaluation of Sustained Release Capsules of Rivastigmine Tartrate

Rivastigmine tartrate is a cholinesterase inhibitor, used in the treatment of dementia associated with Parkinson’s disease and it is currently available in a capsule form. Hydroxy Propyl Methyl Cellulose (HPMC) is the most important hydrophilic carrier material used for the preparation of oral controlled drug delivery systems due to its high swellability and its significant effect on the release kinetics of an incorporated drug. The present study was designed to prepare sustained release granules of Rivastigmine tartrate by using HPMC as matrix former, Microcrystalline cellulose (MCC) as diluent and Magnesium Stearate as lubricant. Blend of Eudragit co-polymers on different ratio was used to coat the granules. The drug-excipient compatibility studies were carried out by using FT-IR, DSC and XRPD analysis. The results shown that there was no significant interaction between the drug and excipients. Granules were prepared by wet granulation method. The granules were subjected to physico-chemical, drug content and in-vitro drug release studies. The best fit release kinetics was achieved with Higuchi equations followed by first order kinetics from the above results it was concluded that extended release granules of Rivastigmine tartrate can be prepared by using HPMC and also found that coating of granules with Eudragit co-polymers also effective to extend the release of drug.

Design and Optimization of Elanzapine Drug Release with Polyoxazoline Based Hydrogel

Due to the fact that Elanzapine is prescribed orally and by injection for psychotic and schizophrenic disorders, and depending on the type of disease, these people are prevented from swallowing the drug; therefore, checking the injectable form of the drug with controlled release, which increases the release of the drug to one week with a single injection, is important. On the other hand, one of the most important biodegradable polymers that have the adhesive property of Elanzapine is Polyoxazoline, so the aim of this study is to design a slow release system, considering the short half-life of this drug and the need for a large number of doses and the patient's lack of cooperation for treatment. The drug is based on Polyoxazoline, which can reduce the consumption and, consequently, the toxicity and accumulation of the drug in the body. Mathematical heart direction, the forecast of different conditions will be presented, and also obtaining the optimal conditions and the final formulation is one of the main goals of this study. In this research, the release of olanzapine on the matrix loaded with olanzapine, the morphological characteristics of the matrix, the thermal characteristics of the matrix and the rheological characteristics of the matrix have been investigated. The release of olanzapine in the examined gels lasted for more than 168 hours, which was a sign of the slow release system, which is the main goal of this project. Several models were used to investigate the release kinetics of olanzapine, and among them, the Higuchi equation showed the best degree of regression with experimental data. By increasing the percentage of Elanzapine, the process of changes in viscosity goes out of the linear state; on the other hand, the difference between the optimum matrix viscosity of 3 and 4% of Elanzapine is small.

Theoretical insights and implications of pH-dependent drug delivery systems using silica and carbon nanotube

In this paper we have studied the density functional theory of four drugs ibuprofen, alendronate, Sulfasalazine and paracetamol with quartz, propylamine, trimethylamine functionalized quartz and carboxyl modified carbon nanotube. The attractive and repulsive interaction energies between drugs and quartz is obtained at various pH values. The attractive and repulsive energies are well correlated with experimental drug loading and releasing behavior by mesoporous silica nanoparticles. Further, a theoretical model is developed that accounts the electrostatic interaction between silica and drug and the model can predict the drug loading and releasing behavior by silica nanoparticles at various pH values.Sulfasalazine can be taken orally and loaded with trimethyl ammonium functionalized mesoporous silica nanoparticles, which keeps the drug in tact with the carrier in the acidic environment of the stomach and releases it into the neutral or basic medium of the small intestine. Alendronate may be loaded and released from propylamine functionalized mesoporous silica nanoparticles in the ranges of 1–5 and > 8, respectively. Ibuprofen is absorbed in an acidic environment and released in basic conditions for carboxyl modified carbon nanotube. The loading and releasing pH ranges for paracetamol in trimethylammonium functionalized mesoporous silica nanoparticles are 4–8 and >8, respectively.We also convert the pH-dependent variant of the diffusion-controlled Higuchi equation. We have changed the original Higuchi equation to produce the pH-dependent variation by incorporating the Nernst-Planck equation into Flick's first law. The updated equation could be used to forecast when medication particles with varying release times will emerge from a nanoparticles matrix.

Dual-Functional Drug Delivery System for Bisphosphonate-Related Osteonecrosis Prevention and Its Bioinspired Releasing Model and In Vitro Assessment.

Clindamycin (CDM)/geranylgeraniol (GGOH)-loaded plasma-treated mesoporous silica nanoparticles/carboxymethyl chitosan composite hydrogels (CHG60 and CHG120) were developed for the prevention of medication-related osteonecrosis of the jaw associated with bisphosphonates (MRONJ-B). The pore structure and performances of CHGs, e.g., drug release profiles and kinetics, antibacterial activity, zoledronic acid (ZA)-induced cytotoxicity reversal activity, and acute cytotoxicity, were evaluated. The bioinspired platform mimicking in vivo fibrin matrices was also proposed for the in vitro/in vivo correlation. CHG120 was further encapsulated in the human-derived fibrin, generating FCHG120. The SEM and μCT images revealed the interconnected porous structures of CHG120 in both pure and fibrin-surrounding hydrogels with %porosity of 75 and 36%, respectively, indicating the presence of fibrin inside the hydrogel pores, besides its peripheral region, which was evidenced by confocal microscopy. The co-presence of GGOH moderately decelerated the overall releases of CDM from CHGs in the studied releasing fluids, i.e., phosphate buffer saline-based fluid (PBB) and simulated interstitial fluid (SIF). The whole-lifetime release patterns of CDM, fitted by the Ritger-Peppas equation, appeared nondifferentiable, divided into two releasing stages, i.e., rapid and steady releasing stages, whereas the biphasic drug release patterns of GGOH were observed with Phase I and II releases fitted by the Higuchi and Ritger-Peppas equations, respectively. Notably, the burst releases of both drugs were subsided with lengthier durations (up to 10-12 days) in SIF, compared with those in PBB, enabling CHGs to elicit satisfactory antibacterial and ZA cytotoxicity reversal activities for MRONJ-B prevention. The fibrin network in FCHG120 further reduced and sustained the drug releases for at least 14 days, lengthening bactericidal and ZA cytotoxicity reversal activities of FCHG and decreasing in vitro and in ovo acute drug toxicity. This highlighted the significance of fibrin matrices as appropriate in vivo-like platforms to evaluate the performance of an implant.

Lincomycin HCl-Loaded Borneol-Based In Situ Gel for Periodontitis Treatment.

Solvent exchange-induced in situ forming gel (ISG) has emerged as a versatile drug delivery system, particularly for periodontal pocket applications. In this study, we developed lincomycin HCl-loaded ISGs using a 40% borneol-based matrix and N-methyl pyrrolidone (NMP) as a solvent. The physicochemical properties and antimicrobial activities of the ISGs were evaluated. The prepared ISGs exhibited low viscosity and reduced surface tension, allowing for easy injection and spreadability. Gel formation increased the contact angle on agarose gel, while higher lincomycin HCl content decreased water tolerance and facilitated phase separation. The drug-loading influenced solvent exchange and matrix formation, resulting in thinner and inhomogeneous borneol matrices with slower gel formation and lower gel hardness. The lincomycin HCl-loaded borneol-based ISGs demonstrated sustained drug release above the minimum inhibitory concentration (MIC) for 8 days, following Fickian diffusion and fitting well with Higuchi's equation. These formulations exhibited dose-dependent inhibition of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 8739, and Prophyromonas gingivalis ATCC 33277, and the release of NMP effectively inhibited Candida albicans ATCC 10231. Overall, the 7.5% lincomycin HCl-loaded 40% borneol-based ISGs hold promise as localized drug delivery systems for periodontitis treatment.

Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

Application of TOPSIS algorithm in describing bacterial cellulose-based composite hydrogel performance in incorporating methylene blue as a model drug

A multi-component hydrogel was developed using bacterial cellulose, alginate, and gelatin with the aid of glycerol as trihydric alcohol which participates in re-distribution of hydrogen bonds in the test system. FTIR, XRD, SEM, and TGA as instrumental techniques were used to structurally characterize the physical/chemical properties of the formed composite hydrogel. By using an exponential equation, swelling behavior of the hydrogel was evaluated. By incorporating a model drug (methylene blue—MB) in the formed hydrogel, experiments were directed to study release characteristics of the MB where the medium solution for the release was prepared at four different pHs. The maximum cumulative drug release at pH 2.8, 6, 7.4, and 9 were 42.8, 63, 80, and 84.5%, respectively. Data fitting process was carried out using five kinetic models (Korsmeyer-Peppas, Higuchi, Hopfenberg, zero-order, and first-order equations) and the preferred kinetic model at each pH was estimated by applying TOPSIS algorithmic technique. The adsorption capacity of the hydrogel in relation to MB was determined while thermodynamic properties of this relationship were quantified (Delta{text{H}}_{text{ad}}^{0}= text{ } -text{99.95 kJ} , {text{mo}}{text{l}}^{-{1}} and Delta{text{S}}_{text{ad}}^{0}= -text{0.237 kJ} , {text{mo}}{text{l}}^{-{1}} {text{K}}^{-{1}}). The results of the present study were in favor of the potential usage of the developed composite hydrogel in drug delivery systems.

Cellulose Nanocrystals (CNCs) and Its Modified Form from Durian Rind as Dexamethasone Carrier.

In this study, CNCs were extracted from durian rind. Modification to CNCs with saponin was conducted at 50 °C for one h. CNCs and CNCs-saponin were employed as dexamethasone carriers. Modification to CNCs using saponin did not change the relative crystallinity of CNCs. CNCs' molecular structure and surface chemistry did not alter significantly after modification. Both nanoparticles have surface charges independently of pH. Dexamethasone-released kinetics were studied at two different pH (7.4 and 5.8). Higuchi, Ritger-Peppas, first-order kinetic and sigmoidal equations were used to represent the released kinetic data. The sigmoidal equation was found to be superior to other models. The CNCs and CNCs-saponin showed burst release at 30 min. The study indicated that cell viability decreased by 30% after modification with saponin.

CURCUMIN IN SITU GEL FOR LOCAL TREATMENT OF PERIODONTITIS: PREPARATION, IN VITRO EVALUATION AND CLINICAL ASSESSMENT

Periodontitis is one of the most widespread oral inflammatory infectious diseases affecting the oral cavity. This study aims to develop and characterize a more effective syringeable curcumin in situ gel for the treatment of periodontitis and evaluate its clinical effectiveness. Curcumin in situ gel was formulated by the cold method using temperature-sensitive (Poloxamer 188, 407), pH-sensitive (Carbopol 934P), and ion-sensitive (Gellan gum) polymers. Gel formulations including Poloxamer 407 and Carbopol 934P as independent factors for the selected response like viscosity and gelation temperature were optimized using central composite design (CCD). All the formulation evaluations were made to ascertain drug content, gelation temperature, viscosity, stability, and in vitro drug release. Appropriate physical characteristics for most formulations and their suitability for periodontitis were observed. Appropriate gelation temperature was found to range from 30.2 to 36.5 o C, with a pH of 6.14 to 7.25. The viscosity of the gel at 4 o C ranged from 12540 to 32400 centipoise. In all cases, the designed formulations were found to be successfully syringeable with a 21-gauge needle at cold temperature. Most of the formulations showed a greater correlation with the Higuchi equation, supporting the assumption that diffusion was the primary mechanism of drug release. Clinical study of the optimized gel formulation revealed a substantial reduction in the clinical markers of periodontitis. The study shows that curcumin in situ gel may be considered as a promising delivery mode for the safe and efficient treatment of periodontitis which substantially overcomes the drawbacks of conventional therapy.

Novel Mucoadhesive Wafers for Treating Local Vaginal Infections.

Current vaginal formulations, such as gels and pessaries, have limitations, including poor retention. Therefore, the use of mucoadhesive formulations that adhere to the vaginal wall would allow prolonged retention and controlled drug release while reducing the required dose and the potential toxicity associated with high drug loading. The aim of the current research was to develop, characterize, and optimize freeze-dried wafers loaded with metronidazole (MTz) to treat vaginal bacterial infections. Blank (BLK) composite wafers comprising carrageenan (CARR) and sodium alginate (SA) were initially formulated; however, due to poor physico-chemical properties, Carbopol (CARB), hydroxypropylmethylcellulose (HPMC), and polyethylene glycol 200 (PEG) were included. The MTz-loaded formulations were obtained by loading optimized composite CARB:CARR- or CARB:SA-based gels (modified with HPMC and/or PEG) with 0.75% of MTz prior to freeze-drying. The physico-chemical properties were investigated using texture analysis (resistance to compressive deformation and adhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), and attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy. Functional properties were investigated by examining the swelling, porosity, drug release, and in vitro antimicrobial activity using E. coli as a model infection-causative agent. The results showed that HPMC and PEG generally improved the wafer's appearance, with smoother surfaces for easy insertion. From the physico-chemical characterization studies, only two composite wafers prepared from 8% CARB:SA 1:4 and 8% CARB:SA 1:9 gels were deemed optimal and loaded with MTz. Both formulations showed sustained drug release and achieved almost 100% cumulative release within 72 h in simulated vaginal fluid. The data obtained from the drug dissolution (release) experiments were fitted to various mathematical equations and showed the highest correlation coefficient with the Higuchi equation, suggesting a drug release based on diffusion from a swollen matrix; this was confirmed by the Korsmeyer-Peppas equation. The released MTz inhibited the growth of the E. coli used as a model bacterial organism.

Release of bupivacaine from artificial ligament implants modified with the silica coating

Post-operative pain is an important health problem that may delay patients' rehabilitation. In surgery, to treat pain, local anesthetics such as bupivacaine are used to effectively reduce post-operative discomfort. The aim of this study was to investigate the release of the bupivacaine from proposed implants and to test the storage stability of implants. The implants were obtained using sol-gel method and the release of the bupivacaine was carried out employing apparatus flow through cell connected to the UV–Vis spectrophotometer. The absorbance of the acceptor fluid was obtained at selected time intervals and the amount of the drug released was calculated. The obtained release profiles were analyzed employing the zero-, first-, second-order kinetics and Higuchi, Korsmeyer-Peppas and Hixon-Crowell models. Based on these equations the release rate constants and the half release time as well as the coefficient of determination were calculated. It was found that the model that the best described the release profile of bupivacaine was zero-order or Higuchi equation. All release profiles were also characterized well by Hixon-Crowell model. The dissolution profiles of the drug were compared deriving the difference factor f1 and the similarity factor f2. The comparison was also carried out employing the statistical methods such as ANOVA with Tukey's HSD test and Student's t-test. It was revealed that all compared release profiles were different. The observed discrepancies between bupivacaine dissolution profiles were connected with the coating preparation. The storage study of I5 implants showed that the amount of bupivacaine released after 6 months of storage was lower indicating the possibility of its decomposition.

De novo synthesis of a MIL-125(Ti) carrier for thermal- and pH-responsive drug release.

Microporous round cake-like (diameter: 900±100nm) MIL-125(Ti) carrier with a central metal (Ti) exhibiting bio-affinity and possessing a great potential to be used as drug release platform, has been synthesized in the present study. The thermal and pH responsiveness of drug delivery systems (DDS) are the most important parameters for drug release and can be provided through polymer coating techniques. The Pluronic F127 (F127) and chitosan (CH) monomers were inserted into the crystal lattice of MIL-125(Ti) carrier during the de novo synthesis process, which were subsequently loaded with doxorubicin (DOX). The results reveal particle size changes (ranged between 30 and 50%) from the original size of the MIL-125(Ti) carrier in response to temperature and pH when the carrier reaches acid environment. The drug release profiles have been completed through self-design device, which provides for the real-time release in the DOX amounts via UV-Vis spectra. The kinetics analysis was used to evaluate the R2 values of first order, Higuchi, Korsmeyer-peppas, and Weibull fitting equations, where the Weibull fitting indicated the best R2. An increase by 59.3% of DOX released under the acid status (pH=5.4) was observed, indicating that the CH-MIL-125(Ti) carrier is temperature and pH responsive. Moreover, the lattice explosion resulting from the temperature increase in the range of 25-42°C caused an increase in F127-MIL-125(Ti) by 30.8-38.3%. The simulated SAXS/WAXS studies for the microstructures of MIL-125(Ti) based DDS at different temperatures after polymer coating (F127-MIL-125(Ti)) provide the possible mechanism of lattice explosion. As such, the responsive Ti-MOF has a highly potential for use in the applications of cancer treatment.

Formulation and evaluation sustained and immediate release bilayer tablet of telmisartan and amlodipine

The study was undertaken with the aim to Formulation and evaluation of bilayer tablet formulation of Telmisartan and Amlodipine. Thus, from the results, it is concluded that the formulation of immediate release layer of Amlodipine using 4-2% concentration of Crospovidone & PVA K30 and 30-20-1.5% concentration of HPMC K 100M-HPMC K4 M-HPMC K15 M are considered as ideal for optimized bilayer tablet formulation. The drug release data of the Telmisartan and Amlodipine was fitted into various kinetic models which as shown in figures 3.8 and 3.11. The order of release of drug was found to be zero order, in which R2 value was close to 1. The n value of Korsmeyer Peppas equation was found to be 0.746. Good correlation coefficients are obtained for Higuchi equation. The results showed that the formulation followed Peppas Model release. Thus, this optimized bilayer tablet formulation can be successfully used in the treatment of hypertension. This modified release bilayer tablets also reduced dosing frequency, increase the bioavailability and provide better patient compliance. From the results it was found that formulation F4 was the best formulation amongst the 5 formulations.