Dissolution Test Research Articles

Development and Validation of Dissolution Test Method for Herbal Medicine Containing Ginsenosides

Background and objective: This study aimed to develop a dissolution test method for quality control of commercial 40% ethanol extract of ginseng-containing dosage forms.Methods: Through preliminary dissolution testing of the commercial dosage forms, suitable parameters for HPLC (high performance liquid chromatography) analysis were determined, including an injection volume of 50 μL and a dissolution time of 1 hour. Additionally, the stability testing of the solution enabled the selection of an appropriate dissolution medium, pH 4.0 buffer solution. Method validation was carried out using reference standard of eight ginsenosides (Rg1, Re, Rf, Rg2, Rb1, RC, Rb2, Rd), indicative components of ginseng, under the selected testing conditions. The evaluation of method validation encompassed specificity, accuracy, precision, and linearity as assessment criteria.Results: The accuracy assessment revealed that the average recovery rates within a 95% confidence interval were appropriate for all ginsenosides, ranging from 98.25% to 101.17%. The precision evaluation, conducted at an intermediate concentration of 8 μg/mL (n = 6), demonstrated relative standard deviations of 0.25% to 1.08%, which met the criterion of being below 2%. The linearity assessment showed that the coefficient of determination (R²) values for all ginsenosides exceeded 0.999, indicating excellent linearity. The quantification limits ranged from 0.32 to 1.09 μg/mL, confirming their suitability for dissolution assessment of the respective formulation. Employing the selected dissolution test method, the dissolution profiles of most ginsenosides in the commercially available ginseng-containing dosage forms reached their maximum values within 60 minutes. No significant differences were observed in results beyond 120 minutes, confirming that a dissolution time of 60 minutes is appropriate for this dosage form.Conclusion: The established method holds promise as a valuable tool for quality control of pharmaceuticals containing ginseng, including those previously unassessed, contributing to future applications in the pharmaceutical industry.

Assessment of the pharmaceutical quality of various brands of omeprazole capsules

Introduction: Omeprazole is a first-line therapy drug for the treatment of peptic ulcer disease. The availability of numerous generic brands in the market raises doubts about their quality. Purpose: This study aimed to assess the pharmaceutical quality of various brands of omeprazole capsules marketed in three states of southern Nigeria. Methods: Organoleptic and physicochemical properties of ten (10) generic brands of omeprazole capsules were assessed according to official and unofficial standards. Quality assurance tests such as weight uniformity, disintegration time and drug content assay were carried out. The dissolution test was done in a double dissolution medium consisting of 0.1 N HCl for 1.0 h and phosphate buffer pH 6.8 for 2.0 h. Results: Capsules tested were suitably packaged with shells containing evenly coloured white pellets. All capsules were slightly soluble in water, sparingly soluble in ethanol and readily dissolved in alkaline medium. The 10 brands tested met the British Pharmacopeia (BP) specification for weight uniformity. All capsules had drug content within 90 - 110% and an average disintegration time of less than 15 min. All brands retained the drug in acid medium for 1 hour but released more than 75% within 40 min in phosphate buffer pH 6.8. Conclusion: Brands of omeprazole capsules passed Pharmacopeia tests, exhibited similar in vitro drug release profiles and may therefore be used interchangeably for the treatment of peptic ulcer. The study also showed that almost all brands of omeprazole capsules available in Nigeria are imported, hence the need arises for regular post-clinical analysis of imported drugs. Keywords: Omeprazole, generic brands, quality, analysis

다공성의 콜로이드성 이산화규소를 이용한 닐로티닙 함유 고형의 자가미세유화 약물전달시스템의 개발

The objective of this study was to develop a novel nilotinib HCl-loaded solidified self-nanoemulsifying drug delivery system (SNEDDS) formulation with enhanced solubility and dissolution rate. Various oils and surfactants were screened, resulting in the selection of Peceol (oil) and Tween 80 (surfactant) and Transcutol P (co-surfactant). Pseudoternary phase diagram was constructed to detect the nanoemulsion zone. Among the SNEDDS formulations tested, the SNEDDS consisting of Peceol (oil), Tween 80 (surfactant), and Transcutol P (co-surfactant) at a weight ratio of 30/50/20 produced an emulsion droplet size of 182.1±1.0 nm. The spray drying technique, using mesoporous silicon dioxide as an inert carrier, was employed to solidify the selected nilotinib HCl-loaded SNEDDS. The resulting nilotinib HCl-loaded solid SNEDDS (S-SNEDDS) was characterized by scanning electron microscopy (SEM), powder X-ray diffractometry (PXRD), dynamic light scattering, saturation solubility and in vitro dissolution study. The S-SNEDDS produced an emulsion droplet size of 185.2±0.9 nm and there was no change in emulsion particle size upon the addition of drug. SEM and PXRD results suggested that nilotinib HCl existed in an amorphous form in nilotinib HCl-loaded S-SNEDDS. Solubility tests across various pH levels showed a significant improvement in nilotinib HCl solubility. Similarly, dissolution tests demonstrated enhanced dissolution rates in all tested solutions, consistent with the solubility results. These results indicate that the employed methodologies were effective in increasing both the solubility and dissolution rates of nilotinib HCl across different pH environments, suggesting a successful enhancement of its bioavailability.

Design and optimization of chitosan-alginate nanoparticles for plant growth hormone indole-3-acetic acid

Excessive use of agrochemicals can lead to environmental degradation, and thus, a potential solution is to control their release using biodegradable polymeric nanoparticles. This study aimed to fabricate indole-3-acetic acid chitosan/alginate nanoparticles (IAA-CANPs) through o/w emulsification and ionotropic gelation, employing a Box-Behnken design (BBD) to evaluate the influence of various factors (alginate: chitosan mass ratio (ALG:CS), TweenTM 80, and IAA concentration) on particle size, zeta potential, and encapsulation efficiency (EE). Response surface methodology (RSM) was used to determine the optimum conditions for nanoparticle fabrication, which were ALG:CS mass ratio of 1:0.10, TweenTM 80 of 1.5% w/v, and IAA of 15 mg/mL. The IAA-CANPs produced under these optimal conditions exhibited an average particle size of 275 ± 19 nm, a polydispersity index (PDI) of 0.37 ± 0.9, a zeta potential of -23.8 ± 0.8 mV, and an EE of 68.5 ± 1.4%. The IAA-CANPs also demonstrated superior physico-chemical stability under UV irradiation exposure compared to free IAA. The IAA-CANPs had stability up to 3 months at 4°C. The release pattern in dissolution media at pH 5.5 and 7.5 indicated a sustained-release behavior, which fit well with the Peppas-Sahlin kinetic model, indicating anomalous diffusion, a non-Fickian diffusion mechanism. These findings suggest that CANPs could be a promising approach for encapsulating and controlling the release of IAA, exhibiting excellent physicochemical stability and potential for agricultural applications.

Elucidating the effect of salt incorporation in tablets on tablet disintegratability

The disintegration of tablets plays a crucial role in facilitating drug release, and disintegrants are used in tablet formulations to promote the disintegration process. This study aimed to explore and understand the impact of salt incorporation on tablet disintegratability. The study was designed to modulate the microenvironment temperature of tablets through dissolution of salts incorporated in the formulation, with the aim to facilitate tablet disintegration. It was observed that the incorporation of salts generally prolonged tablet disintegration. The impact of incorporating salts on tablet properties was both concentration-dependent and multi-factorial. The observed effect of salts on tablet disintegration was likely influenced by a combination of factors, including different properties of the salts, enhanced solubility of components, the temperature difference between the tablet and the disintegration medium, the expansion of air resulting from increased microenvironment temperature, and the competition for water between salts and disintegrants. These factors collectively contributed to the overall impact of salts on tablet disintegration.

Preparation and Evaluation of Azithromycin as Rectal Suppository to Treat Bacterial Infection of COVID-19

In this study azithromycin was formulated for the first time as co-amorphous system suppository system to achieve the maximum bioavailability and to avoid the side effect that might be with oral route which is associated with this drug during treatment of Corona virus secondary bacterial infection. In this study the co-amorphous system was characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (PXRD) and Fourier Transform Infrared Spectroscopy (FTIR). Eight different suppository formulas were prepared, these formulas were subjected to the dissolution test by Ph. Eur. Apparatus I (basket apparatus). The antibacterial activity was measured by the agar well-diffusion method. The results revealed the formation co-amorphous system. The formula in co-amorphous system with glycerin showed the best release for both azithromycin and curcumin. The combination and co-amorphous system showed double value of zone of inhibition rather than the drugs alone. This study will be interested in drugs company to find alternative rout of drug administration for serious infection that associated with GIT symptoms.

Effects of Apex Size on Dissolution Profiles in the USP II Paddle Apparatus

The use of apex vessels may solve coning problems associated with dissolution testing. However, excessive dissolution acceleration can reduce the discriminatory power. This study aimed to clarify how different apex vessel sizes affect the dissolution behavior of cone-forming formulations. Five apex vessels with different heights, centralities, and compendial vessels were used. The paddle rotation speed at which the coning phenomenon resolved was measured using standard particles of different densities. Three model formulations—USP prednisone tablets, atorvastatin calcium hydrate tablets, and levofloxacin fine granules—were selected, and dissolution tests were conducted at 30–100 revolutions per minute (rpm). Compared to the compendial vessels, the disappearance of standard particles at the apex base at lower paddle speeds in apex vessels was observed. Standard particles tended to remain in the center of the apex vessels and disappear at rotational speeds comparable to those of the compendial vessels. Dissolution increased in an apex height-dependent manner in the model formulations, except for the atorvastatin calcium hydrate tablets at 50 rpm. For levofloxacin fine granules, dissolution was also improved by reducing the paddle agitation speed to 30 rpm in the compendial vessels. Differences in apex centrality by 3 mm did not affect the dissolution rate. Our results indicate that apex vessels with low apex heights have a mount-resolving effect, but the degree of dissolution improvement by avoiding the coning phenomenon depends on the formulation characteristics used in the dissolution tests.Graphical abstract

Dissolution Method for Estimation of Deflazacort in Tablet Dosage Form by UV Visible Spectroscopy

The present study describes the development and validation of multimedia dissolution method by UV- Visible Spectroscopy to evaluate the dissolution behavior of deflazacort tablets. The different dissolution media selected for this study are water, 0.1N HCl, pH 4.5 acetate buffer and pH 6.8 phosphate buffer. Spectra of deflazacort in different dissolution media were recorded in range of 200-400nm and 247nm selected as maximum absorptive point. Stability and solubility of deflazacort in different dissolution media i.e., water,0.1 N HCL, pH 4.5 acetate buffer, pH 6.8 phosphate buffer were also studied. Based on this, dissolution medium containing 0.1 N HCL, water and pH 4.5 acetate buffer were found suitable to ensure chemical stability of the deflazacort. The established dissolution conditions were 1000ml dissolution medium, apparatus USP II (paddle), agitation speed 50 RPM for 75 minutes and it is corresponding to>90 % drug release within 60min. The method was validated according to ICH guideline that include accuracy, precision, specificity/selectivity and linearity. Hence, it could be concluded that the developed method can be used as dissolution method for estimation of release of deflazacort in tablet dosage form.

One-Step Preparation of Fiber-Based Chlorzoxazone Solid Dispersion by Centrifugal Spinning.

An amorphous fiber-based solid dispersion of chlorzoxazone was prepared for the first time by employing centrifugal spinning, using polyvinylpyrrolidone as the fiber-forming polymer. After optimization of the spinning parameters, the obtained fibers were characterized using a set of analytical techniques, both in a solid- and solution-state. Morphological characterization revealed a slightly aligned, defect-free fibrous structure with an average fiber diameter of d = 3.07 ± 1.32 μm. The differential scanning calorimetric results indicated a crystalline-to-amorphous transition of the active substance during the centrifugal spinning process, while gas chromatographic determinations revealed a residual ethanol content of 0.42 ± 0.04%. UV spectroscopy indicated the incorporation of chlorzoxazone in the fibrous structures, with an average active substance content of 15.91 ± 0.36 w/w%. During small-volume dissolution studies, the prepared fiber mats presented immediate disintegration upon contact with the dissolution media, followed by rapid dissolution of the active substance, with 84.8% dissolved at 1 min and 93.7% at 3 min, outperforming the micronized, pure chlorzoxazone. The obtained results indicate that centrifugal spinning is a low-cost, high-yield, viable alternative to the currently used methods to prepare fiber-based amorphous solid dispersions of poorly soluble drugs. The prepared chlorzoxazone-loaded microfibers could be used as a buccal dosage form for the systematic delivery of chlorzoxazone and could potentially lead to a rapid onset of action and longer efficacy of the muscle relaxant drug.

Formulation and Evaluation of Insulin-Loaded Sodium-Alginate Microparticles for Oral Administration.

The development of oral insulin drug delivery systems is still an ongoing challenge for pharmaceutical technology researchers, as the formulation process has to overcome a number of obstacles due to the adverse characteristics of peptides. The aim of this study was to formulate different sodium-alginate microparticles as a possible method for oral insulin administration. In our previous studies, the method has been successfully optimized using a small model peptide. The incorporation of insulin into alginate carriers containing nonionic surfactants has not been described yet. In order to enhance the absorption of insulin through biological barriers, Labrasol ALF and Labrafil M 2125 CS were selected as permeation-enhancing excipients. They were applied at a concentration of 0.10% (v/v%), along with various combinations of the two, to increase oral bioavailability. Encapsulation efficiency showed sufficient drug incorporation, as it resulted in over 80% in each composition. In vitro dissolution and enzymatic stability test results proved that, as a pH-responsive polymer, alginate bead swelling and drug release occur at higher pH, thus protecting insulin against the harsh environment of the gastrointestinal tract. The remaining insulin content was 66% due to SIF degradation after 120 min. Permeability experiments revealed the impact of permeation enhancers and natural polymers on drug absorption, as they enhanced drug transport significantly through Caco-2 cells in the case of alginate microparticle formulations, as opposed to the control insulin solution. These results suggest that these formulations are able to improve the oral bioavailability of insulin.

Long-Acting Injectable Antipsychotics-A Review on Formulation and In Vitro Dissolution.

Long-acting injectable (LAI) neuroleptics constitute an effective therapeutical alternative for individuals suffering from persistent mental illness. These injectable pharmaceuticals help patients manage their condition better and improve long-term outcomes by preventing relapses and improving compliance. This review aims to analyse the current formulation aspects of LAI neuroleptics, with particular emphasis on analysis of drug release profiles as a critical test to guarantee drug quality and relevant therapeutical activity. While there is no officially approved procedure for depot parenteral drug formulations, various dissolution tests which were developed by LAI manufacturers are described. In vitro dissolution tests also possess a critical function in the estimation of the in vivo performance of a drug formulation. For that reason, thorough inspection of the in vitro-in vivo correlation (IVIVC) is also discussed.

Experimental study on the influence mechanism of clay particles on the microbial treatment of granite residual soil

The content of clay particles has a key influence on the physical and mechanical properties of microbial solidified granite residual soil. Microbial-induced calcite precipitation (MICP) treatment method of “mixing + grouting” was used to prepare microbial solidified granite residual soil samples with different clay contents and to explore the influence of clay content on the reinforcement effect of microbial solidified granite residual soil. A series of direct shear tests, disintegration tests, and microscopic observation tests was conducted to quantitatively analyze the influence of clay content on the shear strength and disintegration resistance of microbial solidified granite residual soil. The conclusions are summarized as follows: the shear strength and disintegration resistance of granite residual soils solidified by MICP treatment were remarkably improved, with the shear strength increasing by 9%∼16% when the clay content varied from 10%∼40%. The internal friction angle of the granite residual soil with different clay contents increased and then decreased with the increase in clay content. The cohesion of the microbial solidified granite residual soil increased with the increase in clay content, and the internal friction angle reached a minimum of 20% clay content (17.27°), which is 31.85% lower than that of 0% clay content (25.34°). The cohesion of the microbial solidified granite residual soil reached a maximum of 40% clay content (39.54 kPa), which is 8.69 times higher than that of 0% clay content (4.55 kPa). The MICP treatment technology is capable of effectively improving the shear strength and disintegration resistance of granite residual soils. The MICP treated process produces calcium carbonate precipitates that link the sand particles and fill the pores between the soil particles, increasing the number of larger agglomerates in the granite residual soil, which is the essential reason for the improvement in the softening and disintegration of the granite residual soil when exposed to water.

A simple and rapid method for evaluating the disintegration performance of compound fertilizer

ABSTRACT Rapid determination of the dissolution behavior of a compound fertilizer is difficult in agricultural industry. In this work, we describe a simple and rapid method for quantifying the disintegration properties of compound fertilizer for the indirect evaluation of their dissolution. The effects of screen mesh, disintegration time, temperature, fertilizer-water ratio, stacking mode and particle size on fertilizer disintegration test were studied. Under standardized conditions, the maximum and minimum relative standard deviation (RSD) were 12.7% and 0.9%, respectively. The mean deviations of the measured data were > 4%, standard deviations > 4.6%, and interquartile ranges > 6.7%. The feasibility, accuracy, error tolerance, and consistency of this lift disintegration method meet industrial requirements and can be utilized for the rapid determination of the solubility of compound fertilizers.

Thermal activation mechanism and activity evaluation of lithium slag: Insights from simulated hydration

Lithium slag (LS), a by-product of lithium extraction process, is usually stacked on the surface, occupying a significant amount of land area and leading to various environmental concerns. In this study, the pozzolanic activity of LS was improved by the thermal activation method, and its hydration reaction and hydration products were studied under simulated hydration conditions. The changes of macroscopic and microscopic appearance, particle size, chemical composition and chemical bonding of LS were studied at different thermal activation temperatures (0–1100 °C). Subsequently, the activation effects of LS at different temperatures were preliminarily assessed using a dissolution tests, and its hydration process and products were investigated under simulated hydration conditions. Finally, thermally activated LS was used to prepare cement mortar. The results indicated that spodumene decomposition raised the amorphous phase content in LS, thereby enhancing its pozzolanic activity. However, it is important to note that the activity of the amorphous phase in calcined LS was relatively poor and its hydration reaction proceeded at a slow pace. The presence of sulfate in LS was critical for enhancing the 7-d compressive strength of cement mortar. The amorphous phase was contributed to the later strength development of LS-PC mortar. LS activated at 600–700 °C significantly improved the early strength of cement mortar while ensuring better strength development. After 90 d of curing, the compressive strength of LS600 achieved 70 MPa. By understanding these key findings, the amount of LS in cement-based materials can be maximized to improve the comprehensive utilization rate of LS. However, due to the high SO3 content in LS, the influence of LS on the volumetric stability of the cement-based material is still a subject that necessitates further research.

Disintegration behavior and its grading entropy characterization of polyurea modified graded carbonaceous mudstone under loading and drying-wetting cycles

To study the disintegration behavior and characterization indexes of Modified Graded Carbonaceous Mudstone (MGCM), soaking disintegration tests of MGCM under vertical loading and cyclic drying-wetting were carried out with a disintegration test instrument which self-designed by our team. The grain size distribution of MGCM during drying-wetting cycles was analysed. Standard basal entropy, as an important parameter of grading entropy that quantitatively characterizes distribution curves, was introduced to characterize the disintegration behavior of MGCM and correlated with the comprehensive evaluation index, namely, disintegration ratio. The results show that as the number of drying-wetting cycles increases, the Graded Carbonaceous Mudstone (GCM) blocks disintegrate rapidly and the fine-grain content increases. With an increase in vertical load, the particles disintegrate more completely. The contents of each particle group in the GCM test groups stabilize after 9, 7, and 4 drying-wetting cycles under vertical loads of 0, 100, and 200 kPa, respectively. Under the same vertical load of 200 kPa, the contents of each particle group in MGCM test groups with Polyurea (PU) content 0, 5, and 10 wt% stabilize after 4, 6, and 8 drying-wetting cycles, respectively. The inclusion of PU can effectively retard the disintegration of GCM, and the effect is more pronounced with 5 wt% PU content compared to 10 wt%. However, it is also susceptible to the deterioration of PU layer caused by mechanical screen. The grading entropy model of MGCM under loading and cyclic drying-wetting is established. There is a significant positive, linear correlation between the standard basal entropy and the disintegration ratio. A smaller standard basal entropy to a smaller disintegration ratio, indicating a greater degree of particle disintegration and fragmentation. The standard basal entropy can characterize the disintegrated particles of MGCM with different PU content under vertical loading and drying-wetting cycles. The standard basal entropy of GCM decreases rapidly initially and then stabilizes as the number of drying-wetting cycles increases. The standard basal entropy decreases exponentially as the vertical load increases. The results provide a new quantitative index for analyzing the grading characteristics of MGCM following disintegration, which are valuable for engineering construction and disaster prevention in carbonaceous mudstone areas.

Towards a novel pullulan and pullulan-enteric hard capsules: Study of drug release and crucial capsule features

Pullulan, a natural polymer, is often used as a plant-based alternative polymer for gelatin to produce hard capsules. To the best of our knowledge, there have been negligible studies on the performance of enteric pullulan capsules. Hence, this paper describes a new formulation for enteric pullulan hard capsules that can resist the acidic environment of the stomach and release the drug in the small intestine without the need for an exterior coating. This formulation consists of three polymers, including pullulan, Eudragit L100, and κ-carrageenan, which are used to develop resistance against acid and facilitate gelation to form capsules. With regards to the humidity assessment of target hard capsules, it is estimated that the prepared capsules possess an appropriate potential for target utilizations. The capsules were tested using esomeprazole as a model drug for dissolution testing. The results demonstrated that the enteric hard-shell capsules remained stable for 2 h in 0.1 N HCl at a pH of 1.2 and then ruptured upon entering a phosphate buffer (simulated small intestine) medium at a pH of 6.8. The FESEM and cross-sectional analysis revealed that no drug was released due to the absence of pores on the surface. Rheological examinations also revealed that the prepared solution have a desirable property. It is certified that the NMR spectrum proposes the existence of crosslinking and polymerization of pullulan which signifies appropriate existing interactions polymeric binders and gelling agent. TGA and DSC evaluations are in well accordance with the strong cross-linked structure generated by comprising pullulan polymer with the Eudragit pH-sensitive Polymer. Overall. this new formulation has potential feature for utilization in drug delivery systems where controlled release is desired, especially for drugs that are sensitive to acidic environments in the stomach.

Investigation of the binding properties of purified Pentadesma butyracea gum: Anatural alternative to a synthetic polymer

Abstract: The focus of most pharmaceutical research in recent times has been the use of natural products like gums as pharmaceutical excipients because they are safer, economical and readily available. This study aimed to investigate the applicability of gum extracted from the exudates from the stem bark of Pentadesma butyracea as a binder in conventional release tablets using acacia gum as a reference polymer. The purified Pentadesma butyracea gum (PBG) was precipitated from the crude gum mucilage using 96% ethanol. Conventional-release paracetamol tablets were formulated using seven (7) different concentrations of the PBG mucilage (0.5 – 6 %w/w) as a binder via wet granulation (PB1 – PB7). The same approach was used for the reference conventional release paracetamol tablets (AC1- AC7). The drug-excipients and excipients-gum compatibility studies were evaluated using the FTIR. The formulated tablets were evaluated using both pharmacopoeia and non-pharmacopoeia tests. Appropriate mathematical models were used to determine the similarity (f2) and the difference (f1) factors of the dissolution profiles of the test and reference formulations. Granules for batches PB1, AC1, PB2, AC2 and AC3 had fair flow properties, whereas the rest had good flow properties. The FTIR studies showed no interactions between the drug and excipients. All formulations passed the pharmacopoeia and non- pharmacopoeia tests except for formulations PB1, PB2, PB3 and AC1 which failed the friability test, PB1 and AC1 which failed the hardness test, and AC7 which also failed the disintegration test. An increase in gum concentration led to a corresponding increase in the mechanical properties of the tablets. A comparative study showed no significant difference in the hardness and tensile strength of the test and reference tablets. All formulations except PB6 were similar to their reference formulations since f1 > 50 and f2 < 15. In conclusion, the PBG exhibited a good binding property comparable to acacia gum.

Modern approaches to assessing the quality of orally disintegrating tablets

Orally disintegrating tablets (ODTs) are the preferred and accepted solid dosage forms by patients. These tablets disintegrate in the oral cavity within a short period, providing an advantage for individuals who have difficulty swallowing. Quality control of ODTs can be achieved through measures such as friability, porosity, hardness, wetting time, water absorption capacity, in vitro disintegration test, and dissolution test. This article summarizes the advantages and in vitro quality control tests of orally disintegrating tablets.

Fabrication and evaluation of smart pH/thermo dual-responsive injectable intratumoral in situ depot hydrogels for controlled 5-FU delivery

Background5-FU has multiple applications in various cancers but has limitations owing to its shorter half-life and rapid metabolism. In this study, injectable intratumoral gels were developed to enhance 5-FU concentrations in tumor vicinity. Sterile tunable poly (N-isopropylacrylamide)-based pH/thermo dual-sensitive self-assembled and in situ crosslinkable injectable depot gels with low viscous grade of chitosan (LVCS) were developed via cold and free radical polymerization method for localized and sustained delivery.ResultsRheological analysis confirmed the gelation temperature, sol–gel transitions and viscoelastic behavior of in situ gels. Swelling–deswelling–reswelling cycles established the effect of temperature on structural changes. Swelling tests and in vitro drug release conducted in various dissolution media at variable temperatures confirmed pH/thermal dual response of formulations. Methyl thiazolyl tetrazolium assay confirmed that the hydrogels have good cytocompatibility with above 85% cells viability in Vero cells. In vitro cytotoxicity assay against MCF-7 cells displayed that 5-fluorouracil has good anticancer activity in loaded gel form as compared to free 5-FU. The cytotoxic studies showed that IPLVCS-2 and IPLVCS-6 have the highest inhibition (IC50 = 47 ± 1 µg/ml, 34 ± 17 µg/ml) as compared to free 5-FU (IC50 = 52 ± 3 µg/ml).ConclusionCurrent findings conclude that taking the advantage of physiologic environment acidic pH and high temperature of cancer cells, poly(NIPAAm)-g-LVCS formulations can effectively be used as intratumoral controlled depot of 5-FU.Graphical

The Complexity of Bariatric Patient's Pharmacotherapy: Sildenafil Biopharmaceutics and Pharmacokinetics before vs. after Gastric Sleeve/Bypass.

Postbariatric altered gastrointestinal (GI) anatomy/physiology may significantly harm oral drug absorption and overall bioavailability. In this work, sildenafil, the first phosphodiesterase-5 (PDE5) inhibitor, was investigated for impaired postbariatric solubility/dissolution and absorption; this research question is of particular relevance since erectile dysfunction (ED) is associated with higher body mass index (BMI). Sildenafil solubility was determined both in vitro and ex vivo, using pre- vs. postsurgery gastric contents aspirated from patients. Dissolution tests were done in conditions mimicking the stomach before surgery, after sleeve gastrectomy (post-SG, pH 5), and after one anastomosis gastric bypass (post-OAGB, pH 7). Finally, these data were included in physiologically based pharmacokinetic (PBPK) modelling (GastroPlus®) to simulate sildenafil PK before vs. after surgery. pH-dependent solubility was demonstrated with low solubility (0.3 mg/mL) at pH 7 vs. high solubility at pH 1-5, which was also confirmed ex vivo with much lower solubility values in postbariatric gastric samples. Hampered dissolution of all sildenafil doses was obtained under post-OAGB conditions compared with complete (100%) dissolution under both presurgery and post-SG conditions. PBPK simulations revealed delayed sildenafil absorption in postbariatric patients (increased tmax) and reduced Cmax, especially in post-OAGB patients, relative to a presurgery state. Hence, the effect of bariatric surgery on sildenafil PK is unpredictable and may depend on the specific bariatric procedure. This mechanistically based analysis suggests a potentially undesirable delayed onset of action of sildenafil following gastric bypass surgery.