Affect Drug Release Research Articles

Surface analysis of sequential semi-solvent vapor impact (SAVI) for studying microstructural arrangements of poly(lactide-co-glycolide) microparticles.

Biodegradable poly(lactide-co-glycolide) (PLGA) microparticles have been used as long-acting injectable (LAI) drug delivery systems for more than three decades. Despite extensive use, few tools have been available to examine and compare the three-dimensional (3D) structures of microparticles prepared using different compositions and processing parameters, all collectively affecting drug release kinetics. Surface analysis after sequential semi-solvent impact (SASSI) was conducted by exposing PLGA microparticles to different semi-solvent in the liquid phase. The use of semi-solvent liquids presented practical experimental difficulties, particularly in observing the same microparticles before and after exposure to semi-solvents. The difficulties were overcome by using a new sequential semi-solvent vapor (SSV) method to examine the morphological changes of the same microparticles. The SASSI method based on SSV is called surface analysis of semi-solvent vapor impact (SAVI). Semi-solvents are the solvents that dissolve PLGA polymers depending on the polymer's lactide:glycolide (L:G) ratio. A sequence of semi-solvents was used to dissolve portions of PLGA microparticles in an L:G ratio-dependent manner, thus revealing different structures depending on how microparticles were prepared. Exposing PLGA microparticles to semi-solvents in the vapor phase demonstrated significant advantages over using semi-solvents in the liquid phase, such as in control of exposure conditions, access to imaging, decreasing the time for sequential exposure of semi-solvents, and using the same microparticles. The SSV approach for morphological analysis provides another tool to enhance our understanding of the microstructural arrangement of PLGA polymers. It will improve our comprehensive understanding of the factors controlling drug release from LAI formulations based on PLGA polymers.

Cellulose nanofibers as Scaffold-forming materials for thin film drug delivery systems

We explored the potential of cellulose nanofiber (CNF) for designing prolonged-release, thin-film drug delivery systems (TF-DDS). These delivery systems can be used as locally deployable drug-releasing scaffolds for achieving spatial and temporal control over therapeutic concentration in target tissues. Using doxorubicin (DOX) as a model anticancer drug, CNF-based TF-DDS were prepared using different film-formation processes, such as solvent casting and lyophilization. Formulations were prepared with or without the incorporation of additional macromolecular additives, such as gelatin, to include further biomechanical functionality. We studied the films for their mechanical properties, thermal stability, wettability, porosity and in vitro drug release properties. Our experimental results showed that CNF-based films, when prepared via solvent casting method, showed optimized performance in terms of DOX loading, and prolonged-release than those prepared via lyophilization-based fabrication processes. Scanning electron microscopy (SEM) analysis of the CNF-based films showed uniform distribution of fiber entanglement, which provided the scaffolds with sufficient porosity and tortuosity contributing to the sustained release of the drug from the delivery system. We also observed that surface layering of gelatin on CNF films via dip-coating significantly increased the mechanical strength and reduced the wettability of the films, and as such, affected drug release kinetics. The performance of the TF-DDS was evaluated in-vitro against two pancreatic cancer cell lines, i.e. MIA PaCa-2 and PANC-1. We observed that, along with the enhancement of mean dissolution time (MDT) of DOX, CNF-based TF-DDS were able to suppress the proliferation of pancreatic cancer cells in a time-dependent fashion, indicating that the drug liberated from the films were therapeutically active against cancer cells. Additionally, TF-DDS were also tested ex-vivo on patient-derived xenograft (PDX) model of pancreatic ductal adenocarcinoma (PDAC). We observed that DOX released from the TF-DDS was able to reduce Ki-67 positive, pancreatic cancer cells in these models.

Formulation and Evaluation of the In Vitro Performance of Topical Dermatological Products Containing Diclofenac Sodium.

The selection of an appropriate vehicle in a semi-solid topical product is of utmost importance since the vehicle composition and microstructure can potentially cause changes in drug–vehicle or vehicle–skin interactions and affect drug release and subsequent permeation into and across skin. Hence, the aim of this study was to evaluate different semi-solid formulations containing diclofenac sodium for the physicochemical and structural performance of excipients used and various physiological factors governing permeation of drugs applied to skin. The formulations (emulsion, emulgel, gel, and ointment) were prepared using conventional excipients and were found to be homogenous and stable. Rheological analysis demonstrated characteristic shear-thinning and viscoelastic behavior of formulations. The mean release rate of the gel formulation (380.42 ± 3.05 µg/cm2/h0.5) was statistically higher compared to all other formulations. In vitro permeation using human skin showed a significantly greater extent of drug permeation and retention for the emulgel formulation (23.61 ± 1.03 µg/cm2 and 47.95 ± 2.47 µg/cm2, respectively). The results demonstrated that the different formulations influenced product performance due to their inherent properties. The findings of this study demonstrated that a comprehensive physicochemical and structural evaluation is required to optimize the in vitro performance for dermatological formulations depending on the intended therapeutic effect.

Poly(butylene succinate) matrices obtained by thermally-induced phase separation: Pore shape and orientation affect drug release

Poly(butylene succinate) (PBS) scaffolds with 3D microporous interconnected architecture and crystallized PBS substructures have been prepared by thermally-induced phase separation (TIPS). Curcumin (CUR) and piperine (PIP) natural drugs were incorporated into the matrices during a one-step fabrication protocol. Alterations in TIPS parameters such as solvent system (1,4 dioxane (DXN) or THF) and cooling condition (intensity and direction of thermal gradient) affected the phase separation process and the scaffold properties. Controlling the crystallization of DXN in a uniaxial direction, resulted in the formation of microtubular scaffolds with oriented porosities. Well-developed PIP crystals and matrix-integrated CUR agglomerates were uniformly distributed throughout the scaffolds. The integration of CUR to the polymer matrix was confirmed by physicochemical evaluations, attributed to a possible interaction with PBS, resulting in a slower release than PIP. The scaffolds with uniaxially-oriented porosities displayed a greater sustained release (only 50–60% after 170 h) due to the restricted drug diffusion through their dense spherulitic pore walls. Due to such structure and smoother well-arranged surfaces, the oriented scaffolds also exhibited greater biocompatibility. Our results reveal the positive influence of TIPS-derived structural orientation on properties of PBS matrices for cell/drug delivery. • Controlling the porous architecture is crucial to designing cell/drug carriers. • Porosity orientation affects the final properties of the polymeric matrix. • Herein, porosity orientation has been controlled by adjusting TIPS thermal gradient. • Uniaxially-aligned pores had spherulitic and denser walls compared to random ones. • Such a structure could impede the drug diffusion, being achieved a sustained release.

Evaluation of three tropical starches as polymers for the formulation of diclofenac microspheres

Starches are derived from three botanical sources, such as unripe mature banana fruits (Musa sapientum L.), cocoyam (Colocasia esculenta L. Schott), and bitter yam (Dioscorea dumetorum Pax) tubers, have been evaluated as polymers in the design of microspheres incorporating diclofenac sodium as a model drug. Using the ionic gelation process, the starches were pregelatinized and used as polymers in conjunction with sodium alginate to produce diclofenac sodium microspheres with 2% calcium chloride as a crosslinking agent. The morphology, swelling properties, Entrapment Efficiency (EE), and drug release properties of the microspheres were evaluated. Fitting the in-vitro dissolution data into multiple kinetic models yielded the drug release pathways. Spherical discrete microspheres with rough surfaces were obtained with diameters ranging from 580 µm to 670 µm and EEs ranging from 68.0% to 80.7% w/w. For more than 5 hours, diclofenac sodium was released in a controlled manner. The type and concentration of starch in the polymer blend affected drug release from the microspheres, with banana starch at a 4:1 ratio demonstrating the slowest dissolution rate. Drug release from microspheres is best described by the Korsmeyer-Peppas model, which implies that drug release is governed by both diffusion and erosion mechanisms. The finding shows that tropical starches could be used to develop diclofenac sodium microspheres with controlled release.

Sustained Release Biocompatible Ocular Insert Using Hot Melt Extrusion Technology: Fabrication and in-vivo evaluation

Topical eye drops usually have low bioavailability of the drug. Rapid turnover of lacrimal fluid flushes the drug away from the ocular surface, and the drug has limited time for absorption. Therefore, we design Metoprolol loaded ocular insert to enhance bioavailability against glaucoma in this study. Hot-melt extrusion was utilized to prepare the inserts using Gelatin, GelMa, and Polyacrylic acid (PAA) as matrix-forming polymers. The prepared ocular insert was characterized for physicochemical properties and in vitro drug release. It was observed that GelMa concentration and PAA concentration greatly affected drug release. Inserts prepared from Gelatin-PAA released 38.6% Metoprolol in the first hour. However, replacing 20% of Gelatin with GelMa reduced the initial release to 23.6%.Moreover, inserts prepared with 30% GelMa released 19% of the drug in the first hour, which exhibited a quasi zero-order release profile. The effect of PAA concentration on the release of the drug was also very evident. Inserts prepared with 5% PAA concentration released around 30% of the drug in the first hour, while those prepared with 20% PAA took 2 h to release a similar amount of drug. Similarly, 81% and 50% of the drug were released after 4 h from inserts containing 5% PAA and 20% PAA, respectively. Thus, it is clear that Metoprolol release can be tuned by varying the GelMa and PAA concentration in the formulation. The insert, which was able to sustain the drug release for 12 h, has the potential to be used as a good ocular delivery system, which requires less frequent dosing compared to eye drops.

Role of Polymer Concentration and Crosslinking Density on Release Rates of Small Molecule Drugs.

Over the past few years, researchers have demonstrated the use of hydrogels to design drug delivery platforms that offer a variety of benefits, including but not limited to longer circulation times, reduced drug degradation, and improved targeting. Furthermore, a variety of strategies have been explored to develop stimulus-responsive hydrogels to design smart drug delivery platforms that can release drugs to specific target areas and at predetermined rates. However, only a few studies have focused on exploring how innate hydrogel properties can be optimized and modulated to tailor drug dosage and release rates. Here, we investigated the individual and combined roles of polymer concentration and crosslinking density (controlled using both chemical and nanoparticle-mediated physical crosslinking) on drug delivery rates. These experiments indicated a strong correlation between the aforementioned hydrogel properties and drug release rates. Importantly, they also revealed the existence of a saturation point in the ability to control drug release rates through a combination of chemical and physical crosslinkers. Collectively, our analyses describe how different hydrogel properties affect drug release rates and lay the foundation to develop drug delivery platforms that can be programmed to release a variety of bioactive payloads at defined rates.

Impact of polymer crosslinking on release mechanisms from long-acting levonorgestrel intrauterine systems

Polydimethylsiloxane (PDMS) crosslinking density is a critical material attribute of levonorgestrel intrauterine systems (LNG-IUSs) that affects drug release and may have a significant influence on product performance and safety. Accordingly, the objective of the present work was to investigate the impact of PDMS crosslinking on the release mechanisms of LNG-IUSs and thereby achieve better product understanding. To investigate the effect of PDMS crosslinking, LNG-IUSs with varying prepolymer ratios and different mixing conditions were prepared. Accelerated and real-time in vitro release of the LNG-IUSs were conducted for up to 80 days and 7 months, respectively. Contrary to conventional understanding, formulations with higher crosslinking density showed faster drug release rates. To further understand this anomalous release behavior, the microstructure and molecular properties (using scanning electron microscopy, mercury intrusion porosimetry, polymer swelling studies, solid-state silicon NMR, and wide-angle X-ray diffraction) were investigated. Interestingly, it was revealed that high PDMS crosslinking forms a solid-state porous branched network with amorphous polymer domains facilitating fast solvent uptake (in organic solvents) and easy access to the drug particles leading to rapid mass transport of the drug molecules. Furthermore, formulations processed using planetary mixing showed higher crosslinking densities and faster drug release rates than those prepared using manual mixing. Model fitting of all LNG-IUSs were carried out using first order, two-phase (zero order plus Higuchi), and Korsmeyer-Peppas models. The first order model (which showed the best fitting for the full release profile) was used to establish correlations between the drug release rates and the PDMS crosslinking densities of LNG-IUSs. This is the first comprehensive report providing novel insights into crosslinking-induced microstructural changes and physicochemical properties that dictate drug release from LNG-IUSs.

Comparison of PLA-Based Micelles and Microspheres as Carriers of Epothilone B and Rapamycin. The Effect of Delivery System and Polymer Composition on Drug Release and Cytotoxicity against MDA-MB-231 Breast Cancer Cells.

Co-delivery of epothilone B (EpoB) and rapamycin (Rap) increases cytotoxicity against various kinds of cancers. However, the current challenge is to develop a drug delivery system (DDS) for the simultaneous delivery and release of these two drugs. Additionally, it is important to understand the release mechanism, as well as the factors that affect drug release, in order to tailor this process. The aim of this study was to analyze PLA–PEG micelles along with several types of microspheres obtained from PLA or a mixture of PLA and PLA–PEG as carriers of EpoB and Rap for their drug release properties and cytotoxicity against breast cancer cells. The study showed that the release process of EpoB and Rap from a PLA-based injectable delivery systems depends on the type of DDS, morphology, and polymeric composition (PLA to PLA–PEG ratio). These factors also affect the biological activity of the DDS, because the cytotoxic effect of the drugs against MDA-MB-231 cells depends on the release rate. The release process from all kinds of DDS was well-characterized by the Peppas–Sahlin model and was mainly controlled by Fickian diffusion. The conducted analysis allowed also for the selection of PLA 50/PLA–PEG 50 microspheres and PLA–PEG micelles as a promising co-delivery system of EpoB and Rap.

Effect of Polymer Concentration and Crosslinking Time On Drug Release from Microspheres of Mucuna Gum

The study investigated the feasibility of delivering diclofenac sodium in microspheres of mucuna gum and whether polymer concentration and crosslinking time would affect drug release. Diclofenac sodium microspheres were successfully prepared using the chemical and thermal crosslinking method. Gluteraldehyde was used as the crosslinking agent. Thereafter, invitro release of diclofenac sodium from the microspheres was evaluated using simulated intestinal fluid as the medium. Increase in mucuna gum concentration did not delay rate of drug release but increased total cumulative drug released. Increase in crosslinking time slowed down release of the drug from the microspheres, an indication that modification of crosslinking time is important for sustained release. This could contribute towards producing sustained release diclofenac sodium which will improve patient compliance as a result of subsequent reduction in dosing frequency. None of the batches gave 100% drug release. This being the case, drug loading can be modified for optimum therapeutic effect.

Should local drug delivery systems be used in dentistry?

In dentistry, the use of biomaterial-based drug delivery systems (DDS) aiming the release of the active compounds directly to the site of action is slowly getting more awareness among the scientific and medical community. Emerging technologies including nanotechnological platforms are offering novel approaches, but the majority are still in the proof-of-concept stage. This study critically reviews the potential use of DDS in anesthesiology, oral diseases, cariology, restorative dentistry, periodontics, endodontics, implantology, fixed and removable prosthodontics, and orthodontics with a special focus on infections. It also stresses the gaps and challenges faced. Despite numerous clinical and pharmacological advantages, some disadvantages of DDS pose an obstacle to their widespread use. The biomaterial's biofunctionality may be affected when the drug is incorporated and may cause an additional risk of toxicity. Also, the release of sub-therapeutic levels of drugs such as antibiotics may lead to microbial resistance. Multiple available techniques for the manufacture of DDS may affect drug release profiles and their bioavailability. If the benefits outweigh the costs, DDS may be potentially used to prevent or treat oral pathologies as an alternative to conventional strategies. A case-by-case approach must be followed.

Formulation and Evaluation of Medicated Chewing gum consisting of Dextromethorphan and Guaifenesin for the treatment of cough

Common cold is the most frequently recurring disease in the world and is a leading cause of doctor visits and missed days from school and work. Cold reliever medicated chewing gum (MCG) will be a definitive patient acceptable solution for this condition. Dextromethorphan hydrobromide and guaifenesin will be easily released from chewing gum into the salivary fluid within few minutes of chewing and can be easily permeated from oral mucosa by the pressure created by the chewing action and absorbed to a larger extent into the systemic circulation. Therefore, ultimately patients will get quick relief from symptoms of common cold with greater compliance compared to other conventional dosage forms. This study mainly focuses on taste masking of dextromethorphan hydrobromide and guaifenesin with Kyron T-114, its formulation development in the MCG form and its quality and performance evaluation with the study of potential factors affecting drug release by 32 full factorial experimental design. Formulation ingredients, such as elastomers, softeners, bulking agents, play an important role in the feel of the final product and its consistency; while sweeteners and flavours play a very essential character in its sensory properties. Inter individual variation in chewing frequency and chewing intensity is the main factor which affects release of active ingredient from MCG; while salivary dilution and involuntary swallowing are main reasons for variability in the absorption site, i.e., either from buccal mucosa or from gastrointestinal tract.

Mesoporous Silica Nanoparticles of Hydroxyurea: Potentially Active Therapeutic Agents

Background: Present malignant cancer medicines have the advantage of magnetic nanoparticles as delivery carriers to magnetically accumulate anticancer medication in malignant growth tissue. Aim: In the present investigation, a silica nanoparticles (MSNs) stacked with hydroxyurea were combined and was optimized for dependent and independent variables. Methods: In this study, microporous silica nanoparticles stacked with neoplastic medication were prepared through emulsification followed by the solvent evaporation method. Prepared MSNs were optimized for dependent and independent variables. Different formulations were prepared with varying ratios of polymer, lipid and surfactant which affect drug release and kinetics of drug release pattern. The obtained MSNs were identified by FTIR, SEM, drug entrapment, in-vitro drug release, drug release kinetics study, and stability testing in order to investigate the nanoparticle characteristics. Results: The percentage drug entrapment of the drug for the formulations F1, F2, F3 was found to be 27.78%, 65.52% and 48.26%. The average particle size for F2 formulation was found to be 520 nm through SEM. The cumulative drug release for the formulations F1, F2, F3 was found to be 64.17%, 71.82% and 32.68%. The formulations were found to be stable which gives controlled drug delivery for 6 hours. Conclusion: From the stability studies data it can be culminated that formulations are most stable when stored at lower temperature or in refrigerator i.e. 5˚C ± 3˚C. It can be concluded that MSN’s loaded with hydroxyurea is a promising approach towards the management of cancer due to its sustained release and less side effects.

Comprehensive review on characterizations and application of gastro-retentive floating drug delivery system

Current pharmaceutical situation focuses on the preparation of gastro-retentive floating drug delivery system (GRFDDS). This systems has gained noteworthy interest in the past decades. These are the low density systems that float over the gastric contents and remain buoyant in the stomach for a prolonged period of time without affecting the gastric emptying rate. GRFDDS is used to delay the residence time of delivery in stomach. The controlled gastric retention of solid dosage forms may be achieved by the mechanism of mucoadhesion, floatation, sedimentation, expansion, modified shape systems or by the administration of pharmacological agents that delaying gastric emptying. This results in targeting of release of drug at a specific site for the systemic or local effects. GRDDS is used to overcome challenges associated with conventional oral dosage forms and to release the drug at a specific absorption site to improve bioavailability of particular drug substance. Some floating drug delivery systems have shown the capability to accommodate these variations without affecting drug release. This review mainly focuses characterizations and application of gastro-retentive floating drug delivery systems.

Evaluation of Application of Drug Modeling in Treatment of Liver and Intestinal Cancer

In drug delivery systems, mathematical modeling plays an important role in more clearly explaining the important mechanisms of drug release profiles, so as to facilitate the development of new drug products with a regular approach rather than trial and error. Mathematical models related to known drug release mechanisms fall into three categories: infiltration, controlled inflation systems, and erosion. In the case of liposomal nanoparticles as a biodegradable nanocarrier matrix, the release control is by hydrolysis gap in the polymer chain which will lead to matrix erosion, although penetration due to slow erosion may be still predominant. On the other hand, in the case of biodegradable nanocarriers, drug release is due to the concentration gradient either in the penetration or in the penetration enhancement system by erosion. This classification allows mathematical models to be developed in different ways for each type of system. Mathematical modeling of drug release can provide good insight into chemical processes and modes of delivery in drug delivery as well as the effect of design parameters. In both biodegradable and non-biodegradable nanocarriers, design parameters such as drug loading can significantly affect drug release mechanisms. Therefore, the optimized nano-carrier design for the required drug release profile can be predicted using a regular method with a minimum number of experimental studies. Thus, mathematical modeling can help predict drug release rates; as a result, researchers can come up with much more effective drug formulations and more accurate methods that will save time and money.

Optimizing overnight oral appliance for sustained-release varnish delivery system of sirolimus

<h3>Objectives</h3> Intraoral trays can be used to deliver treatment materials and medications for dental or mucosal conditions. Maintaining appropriate salivary levels of the active ingredient is challenging when using local application. We have previously analyzed salivary levels and local effects of slow-release varnishes (with clotrimazole or sirolimus as the active ingredient) during the daytime. The aims of the present study were as follows: (1) to optimize overnight appliances for slow-release medications by measuring saliva and blood levels and (2) to evaluate the safety of overnight use. <h3>Methods</h3> An acrylic tray containing 0.5 mg of sirolimus in a sustained-release varnish was applied to 6 anterior teeth for 12 hours in 10 healthy volunteers. Whole unstimulated saliva was collected 1, 2, 10, and 12 hours after application, and a blood sample was taken after 12 hours. Drug levels were analyzed. Results from slow- and fast-release formulations, varnish application position on the tray (buccal, palatal, or lingual), and tray placement (mandibular vs maxillary) were compared. The volunteers evaluated the varnish and tray. The study was approved the hospital ethics committee. <h3>Results</h3> Salivary sirolimus was undetected with use of the slow formulation. The faster formulation produced salivary concentrations of 0.3-45 ng/mL. The highest salivary levels were observed with a mandibular tray with lingual varnish application (up to 178 ng/mL). The sialometry of all participants was within normal range (0.2-2 mL/min), and the highest drug levels were found when salivary flow was lowest. The medication was undetected in the blood. No local reactions or side effects were reported. <h3>Conclusions</h3> Salivary concentrations of medications delivered using an oral tray can be affected by the release rate of formulation and, more important, by the position of the tray and the varnish within it and salivary flow rate. Overnight oral trays can be used to deliver medications especially when 24-hour drug exposure is desired. Further studies regarding local factors affecting drug release and salivary levels are required.

Formulation Development and Evaluation of New Albendazole Tablets with Integrated Quality by Design (QbD) Approach

Hydatid disease occurs in most areas of the world and currently affects about one million people. Albendazole is an orally administered broad spectrum anthelmintic drug approved by US FDA in 1996. Literature review suggests Albendazole is low solubility compound and most of the studies were performed to improve the solubility with traditional approach of product development. The present study was aimed to apply Design of Experiments (DoE) in the development and optimization of drug release from new Albendazole tablets using three factor two level (23) full factorial designs with integrated Quality be Design (QbD) approach. New Albendazole tablets were formulated using micronized grade of the Albendazole active and excipients were selected inline with market reference product. Quality target product profile (QTPP) and Critical quality attributes (CQAs) were designed. Risk assessment was used to identify the Formulation variables impacting CQA dissolution. The amount of Formulation variables were optimized on the basis of drug release profiles at 15 minutes and 30 minutes of different formulation batches manufactured based on 23 full factorial design. Tablets were prepared by wet granulation technique and evaluated for various physicochemical parameters and in vitro drug release. Formulation trials dissolution results at 15 minutes and 30 minutes were evaluated to derive the concentration of Formulation variables which will achieve the release of more than 80%. Analysis of variance (ANOVA) analysis, Pareto chart and Contour plot were used to predict the values of formulation variables and their effect on dissolution. Updated risk assessment of the Formulation Variables was performed and justification was provided for reduction of risk from medium to low level. Optimized formulation from DOE had comparable dissolution profile with market reference tablet. Stability studies of new Albendazole tablets 200 mg were conducted at ICH accelerated conditions and found to be stable. Thus studies revealed that full factorial experimental design could efficiently be applied for optimization of formulation variables affecting drug release. New Albendazole tablets 200 mg successfully formulated with application of the integrated quality by design (QbD) and design of experiment (DOE) approach and thereby achieved comparable release profile with market reference product.&#x0D;

Controllable release of pirfenidone by polyvinyl alcohol film embedded soft contact lenses in vitro and in vivo

To increase the amount of pirfenidone (PFD) loaded in polyvinyl alcohol (PVA) film embedded soft contact lens (SCL), and evaluate its function of sustaining delivery of drug in vitro and in vivo. Drug loading efficiency within PVA film and SCLs, drug release from SCLs in vitro, and the effects of parameters of SCLs and external environment on drug release in vitro were evaluated by ultraviolet–visible spectrophotometer at 312 nm. Safety of SCLs was evaluated in vitro by transformed human corneal epithelial cell. Safety in vivo was determined by optical coherence tomography and histology of anterior segment of rabbits. Drug release study in tear fluid and aqueous humor were measured by ultra-performance liquid chromatography. SCLs had smooth surface and were fit for experimental rabbits. Amount of PFD in PVA film and SCLs were 153.515 μg ± 12.508 and 127.438 μg ± 19.674, respectively, PFD in PVA film was significantly higher than SCLs (p=.006) and closed to 150 μg (targeting amount of PFD to be loaded). Thickness of SCLs, molecular weight of PVA, and amount of PVA used in SCLs affected drug release in vitro significantly. Thickness of PVA film and amount of drug in SCLs had no effect on drug release rate in vitro. SCLs were safe in vitro and in vivo, PFD released from SCLs could be detected around 12 hours in tears and aqueous humor, and the concentration of drug was higher than eye drop at all detected time points while amount of PFD in SCLs was lower than eye drop. Drug loaded PVA film embedded SCLs may be a promising ocular drug delivery system.

Formulation and Optimization of Biodegradable Periodontal Chips Containing Metronidazole and Levofloxacin

This research aimed to developintrapocket,biodegradablechips ofpoly(d,l-lactide-co-glycolide) (PLGA) loaded with Metronidazole (MZ) and levofloxacin (LF),for sustained release local drug delivery in periodontal pocket to treat periodontitis. Metronidazole and levofloxacin are widely employed for the treatment of periodontitis,but high oral dose and resistance development after long-term oral administration limit their use, hence local delivery is a good approach. The chips were prepared by solvent casting technique using diethyl phthalate as plasticizer. Their physical characteristics, such as drug content,surface pH, swelling index, and folding endurance, exhibited results within limit. Further, FTIR and DSCstudies revealed stability of chips and compatibility between drugs and excipients.In vitro release in McIlvainebuffer pH 7.8 was of sustained nature assisted by the burst effect. Design-Expert® (11.0.4) software was used to study the effect of polymer &amp; plasticizer on release of drugs Polymer concentrationsnegatively affected drug release and positively affected T90 (time for releasing 90% of the drug) due toaltered matrix density. In contrast, the plasticizer concentration increases membrane permeability andhence increased drug release, lowering T90. Forvarious response variables,polynomial mathematical models were generated usingmultiple regression analysis, and found to be statistically significant (????&lt;0.05).The antibacterial efficacy of films was tested on Pseudomonas spp. Bacteroides spp., indicatinggood antibacterial activity. Optimized formulations were further used for preparing optimized biodegradable, Metronidazole-Levofloxacin sustained release chip. Conclusively, the films of MZ and LF were successful tools for the management ofperiodontitis.

Magnetic Resonance Methods as a Prognostic Tool for the Biorelevant Behavior of Xanthan Tablets

Hydrophilic matrix tablets with controlled drug release have been used extensively as one of the most successful oral drug delivery systems for optimizing therapeutic efficacy. In this work, magnetic resonance imaging (MRI) is used to study the influence of various pHs and mechanical stresses caused by medium flow (at rest, 80, or 150 mL/min) on swelling and on pentoxifylline release from xanthan (Xan) tablets. Moreover, a bimodal MRI system with simultaneous release testing enables measurements of hydrogel thickness and drug release, both under the same experimental conditions and at the same time. The results show that in water, the hydrogel structure is weaker and less resistant to erosion than the Xan structure in the acid medium. Different hydrogel structures affect drug release with erosion controlled release in water and diffusion controlled release in the acid medium. Mechanical stress simulating gastrointestinal contraction has no effect on the hard hydrogel in the acid medium where the release is independent of the tested stress, while it affects the release from the weak hydrogel in water with faster release under high stress. Our findings suggest that simultaneous MR imaging and drug release from matrix tablets together provide a valuable prognostic tool for prolonged drug delivery design.