Self-microemulsifying drug delivery system-based gastroretentive in situ raft of pazopanib with enhanced solubility and bioavailability.

Pazopanib hydrochloride (PZH) is a Biopharmaceutics Classification System class II drug that faces challenges at the formulation forefront including low aqueous solubility (0.043 mg/mL) and poor oral bioavailability (14-39%). The present investigation aimed to develop a self-microemulsifying drug delivery system (SMEDDS) of PZH using a blend of Capryol® 90, Labrasol®, and propylene glycol to improve its solubility. Furthermore, a sustained-release SMEDDS-based gastroretentive floating system was developed and optimized using the Central Composite Design approach of DoE. The optimized SMEDDS-based in situ gelling raft, R-SM-PZH, exhibited minimal floating lag time (3.09 ± 0.8 s), optimal viscosity (1229.4 ± 20.9 cP) and density (0.327 ± 0.15 g/mL) as compared to other formulations under study. Additionally, R-SM-PZH was evaluated for its in vitro dissolution in FaSSGF and FeSSGF, pharmacokinetic profile, and MTT assay (against NCI-H460 lung cancer cells) compared to pure PZH. A 12 h sustained release, three-fold augmentation in dissolution rate and bioavailability, and 15-fold enhancement in cytotoxicity were observed in comparison to pure PZH. Thus, the SMEDDS-based in situ gelling raft presents a promising approach to advancing the developability potential of PZH.

Design and fabrication of 3D-printed gastric floating tablets of captopril: effect of geometry and thermal crosslinking of polymer on floating behavior and drug release.

The present study aims to investigate the potential of the 3D printing technique to design gastroretentive floating tablets (GFTs) for modifying the drug release profile of an immediate-release tablet. A 3D-printed floating shell enclosing a captopril tablet was designed having varying number of drug-release windows. The impact of geometrical changes in the design of delivery system and thermal cross-linking of polymers were evaluated to observe the influence on floating ability and drug release. Water uptake, water insolubilization, Differential Scanning Calorimetry (DSC), and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) were performed to assess the degree of thermal cross-linking of polyvinyl alcohol (PVA) filament. The 3D-printed GFT9 was considered the optimized gastric floating tablet that exhibited >12 h of total floating time with zero floating lag time and successfully accomplished modified-drug release by exhibiting >80% of drug release in 8 h. The zero-order release model, with an r2 value of 0.9923, best fitted the drug release kinetic data of the GFT9, which followed a super case II drug transport mechanism with an n value of 0.95. The optimized gastric floating device (GFT9) also exhibited the highest MDT values (238.55), representing slow drug release from the system due to thermal crosslinking and the presence of a single drug-releasing window in the device.

Gastroretentive Delivery Approach to Address pH-Dependent Degradation of (+)- and (-)-Phenserine.

(-)-Phenserine ("phenserine") and (+)-phenserine (posiphen; buntanetap) are longer-acting enantiomeric analogs of physostigmine with demonstrated promise in the treatment of Alzheimer's and Parkinson's diseases. Both enantiomers have short plasma half-lives, and their pharmacokinetics might be improved through the use of either once or twice-daily administration of an extended-release dosage form. Phenserine was observed to form a colored degradation product in near-neutral and alkaline pH environments, and at pH 7, the half-life of posiphen was determined to be ~ 9 h (40 °C). To limit luminal degradation which would reduce bioavailability, a gastroretentive tablet composed of a polyethylene oxide-xanthan gum matrix was developed. When placed in simulated gastric fluid (pH 1.2), approximately 70% of the phenserine was released over a 12 h period, and no degradants were detected in the release medium. In comparison, a traditional hydrophilic-matrix, extended-release tablet showed measurable amounts of phenserine degradation in a pH 7.2 medium over an 8 h release interval. These results confirm that a gastroretentive tablet can reduce the luminal degradation of phenserine or posiphen by limiting exposure to neutral pH conditions while providing sustained release of the drug over at least 12 h. Additional advantages of the gastroretentive tablet include reduced gastric and intestinal concentrations of the drug resulting from the slower release from the gastroretentive tablet which may also limit the occurrence of the dose-limiting GI side effects previously observed with immediate-release phenserine capsules.

Biodegradable Guar-Gum-Based Super-Porous Matrices for Gastroretentive Controlled Drug Release in the Treatment of Helicobacter pylori: A Proof of Concept.

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.

Development of Gastroretentive Carriers for Curcumin-Loaded Solid Dispersion Based on Expandable Starch/Chitosan Films.

Curcumin, a polyphenolic extract from the rhizomes of turmeric, exhibits antioxidant, anti-inflammatory, and anticancer activities, which are beneficial for the treatment of gastric diseases. However, curcumin's therapeutic usefulness is restricted by its low aqueous solubility and short gastric residence time. In this study, curcumin-loaded solid dispersion (ratio 1:5) was prepared using Eudragit® EPO (Cur EPO-SD), resulting in an approximately 12,000-fold increase in solubility to 6.38 mg/mL. Expandable films incorporating Cur EPO-SD were subsequently prepared by solvent casting using different types of starch (banana, corn, pregelatinized, and mung bean starch) in combination with chitosan. Films produced from banana, corn, pregelatinized and mung bean starch unfolded and expanded upon exposure to simulated gastric medium, resulting in sustained release of 80% of the curcumin content within 8 h, whereas films based on pregelatinized starch showed immediate release characteristics. Curcumin-loaded expandable films based on different types of starch exhibited similar cytotoxic effects toward AGS cells and more activity than unformulated curcumin. Furthermore, the films resulted in increased anti-inflammatory activity against RAW 264.7 macrophage cells compared with the NSAID, indomethacin. These findings demonstrate the potential of expandable curcumin-loaded films as gastroretentive dosage forms for the treatment of gastric diseases and to improve oral bioavailability.

Controlled release of MT-1207 using a novel gastroretentive bilayer system comprised of hydrophilic and hydrophobic polymers.

In the present study, novel gastroretentive bilayer tablets were developed that are promising for the once-a-day oral delivery of the drug candidate MT-1207. The gastroretentive layer consisted of a combination of hydrophilic and hydrophobic polymers, namely polyethylene oxide and Kollidon® SR. A factorial experiment was conducted, and the results revealed a non-effervescent gastroretentive layer that, unlike most gastroretentive layers reported in the literature, was easy to prepare, and provided immediate tablet buoyancy (mean floating lag time of 1.5 s) that lasted over 24 h in fasted state simulated gastric fluid (FaSSGF) pH 1.6, irrespective of the drug layer, thereby allowing a 24-hour sustained release of MT-1207 from the drug layer of the tablets. Furthermore, during in vitro buoyancy testing of the optimised bilayer tablets in media of different pH values (1.0, 3.0, 6.0), the significant difference (one-way ANOVA, p < 0.001) between the respective total floating times indicated that stomach pH effects on tablet buoyancy are important to be considered during the development of non-effervescent gastroretentive formulations and the choice of dosing regimen. To the best of our knowledge, this has not been reported before, and it should probably be factored in when designing dosing regimens. Finally, a pharmacokinetic study in Beagle dogs indicated a successful in vivo 24-hour sustained release of MT-1207 from the optimised gastroretentive bilayer tablet formulations with the drug plasma concentration remaining above the estimated minimum effective concentration of 1 ng/mL at the 24-hour timepoint and also demonstrated the gastroretentive capabilities of the hydrophilic and hydrophobic polymer combination. The optimised formulations will be forwarded to clinical development.

Superporous hydrogels based on blends of chitosan and polyvinyl alcohol as a carrier for enhanced gastric delivery of resveratrol.

Resveratrol exhibits a number of pharmacological properties, notably antioxidant, anti-inflammatory and anti-cancer activities which are beneficial for the treatment of gastric diseases. However, the poor aqueous solubility and rapid metabolism are the important limitations in clinical uses. Superporous hydrogels (SPHs) based on chitosan/PVA blends were developed as a carrier for resveratrol solid dispersion (Res_SD) to increase the solubility and achieve sustained drug release in the stomach. The SPHs were prepared by gas forming method using glyoxal and sodium bicarbonate as cross-linking agent and gas generator, respectively. The solid dispersions of resveratrol with PVP-K30 were prepared by solvent evaporation and incorporated into the superporous hydrogels. All formulations showed rapid absorption of simulated gastric fluid and reached the equilibrium swollen state within a few minutes. The water absorption ratio and mechanical strength of SPHs were predominantly affected by the chitosan content, with maximum values at 1400 % and 375 g/cm2, respectively. The Res_SD-loaded SPHs exhibited good floating properties and SEM micrographs revealed a highly interconnected pores structure with size around 150 µm. Resveratrol was efficiently entrapped within the SPHs at levels between 64 and 90 % w/w and efficient drug release was sustained over 12 h dependent on the concentration of chitosan and PVA. The Res_SD-loaded SPHs exhibited slightly less cytotoxic efffect towards AGS cells than pure resveratrol. Furthermore, the formulation showed similar anti-inflammatory activity against RAW 264.7 cells compared with indomethacin.

Formulation and Pharmacokinetic Evaluation of Ethyl Cellulose/HPMC-Based Oral Expandable Sustained Release Dosage of Losartan Potassium.

Prolonged retention of losartan potassium in the upper gastrointestinal tract is anticipated to increase its absorption and exposure to CYP450 enzyme subfamilies, undertaking its conversion to more potent (10-40 times) active metabolite, losartan carboxylic acid (LCA). Consistent with this, hydroxypropyl methylcellulose K4M/ethyl cellulose-based novel expandable films (EFs) containing losartan potassium (LP) suitable for prolonged retention in the stomach were developed. The films were prepared by solvent casting method. USP type II dissolution apparatus (0.1 N HCl, 37°C, 100 rpm) was used to perform the dissolution testing (drug release, unfolding behavior, film integrity, erosion, and water uptake) of the films. In vivo pharmacokinetic studies were carried out in rabbits. An HPLC-UV method was used for the quantification of the drug and its active metabolite in plasma. These folded films placed inside hard gelatin capsule shells unfolded to full dimensions in dissolution medium and provided sustained drug release throughout 12 h. The plasma drug concentration-time curves obtained from the in vivo studies were used to determine pharmacokinetic parameters, such as area under the plasma drug concentration-time curve (AUC), area under first moment curve (AUMC), mean residence time (MRT), Cmax, Tmax, t1/2, ke, and Fr in comparison with that of the market formulation, Cozaar®. The novel EFs significantly changed the pharmacokinetic parameters of the drug and its active metabolite. The apparent elimination rate constant (ke) significantly decreased, while MRT and elimination half-life (t1/2) increased in both cases. The relative bioavailabilities (Fr) of both LP and E3174 using the novel formulation were higher than that of Cozaar®.

Drotaverine Hydrochloride Superporous Hydrogel Hybrid System: a Gastroretentive Approach for Sustained Drug Delivery and Enhanced Viscoelasticity.

This study aims to prepare drotaverine hydrochloride superporous hydrogel hybrid systems (DSHH systems) to prolong its residence time in the stomach, provide extended release and reduce its frequency of administration. Drotaverine hydrochloride (DRH) is a spasmolytic drug that suffers from brief residence due to intestinal hypermotility during diarrheal episodes associated with gastrointestinal colics resulting in low bioavailability and repeated dosing. Eight DSHH systems were prepared using gas blowing technique. The prepared DSHH systems were evaluated regarding their morphology, incorporation efficiency, density, porosity, swelling ratio, viscoelastic property, erosion percentage and release kinetics. The FH8 formula containing equal proportion of chitosan (3%) /polyvinyl alcohol (3%) as strengthener and crosslinked with tripolyphosphate showed the highest incorporation efficiency (91.83 ± 1.33%), good swelling ratio (28.32 ± 3.15% after 24 h), optimum viscoelastic properties (60.19 ± 3.82 kPa) and sustained release profile (88.03 ± 2.15% after 24 h). A bioequivalence study was done to compare the bioavailability of the candidate formula versus Spasmocure®. Statistical analysis showed significant (P < 0.05) increase in bioavailability 2.7 folds with doubled Tmax (4 h) compared to the marketed product (2 h). These results declared that the superporous hydrogel hybrid systems could be a potential gastroretentive approach for the sustained delivery of drugs with short residence time with enhanced viscoelasticity.

Gastroretentive Sustained-Release Tablets Combined with a Solid Self-Micro-Emulsifying Drug Delivery System Adsorbed onto Fujicalin®.

Gastroretentive drug delivery systems (GRDDS) get retained in the stomach for a long time, thus facilitating the absorption of drugs in the upper gastrointestinal tract. However, drugs that are difficult to dissolve or unstable in an acidic environment are not suitable for GRDDS. The current study designs GRDDS combined with a self-micro-emulsifying drug delivery system (SMEDDS) for drugs with solubility or stability problems in the stomach. The model drug fenofibrate was formulated into the optimized liquid SMEDDS composed of 50 w/w% Capryol® PGMC, 40 w/w% Kolliphor® RH40, and 10 w/w% Transcutol® HP and solidified through adsorption on several porous adsorbents. In a dissolution medium at pH 1.2, the powdered SMEDDS using Fujicalin® dissolved quickly and achieved higher drug dissolution than other adsorbents. Based on these results, a gastroretentive bilayer tablet consisting of a drug release layer and a swelling layer was designed. The drug release layer was formulated with the powdered SMEDDS and hydroxypropyl methylcellulose (HPMC) as a release modifier. HPMC was also added to the swelling layer as a water-swellable polymer. The dissolution rate depended on the viscosity of the HPMC in the drug release layer. The time for 90% drug release was extended from 3.7 to 12.0 h by increasing the viscosity grade of HPMC from 0.1 to 100 K. Moreover, the tablet swelled and maintained a size comparable to a human pylorus diameter or more for at least 24 h. This GRDDS could apply to a broader range of drug candidates.

Formulation of metoclopramide HCl gastroretentive film and in vitro- in silico prediction using Gastroplus® PBPK software.

The new trends in pharmaceutical studies focus on targeting drug delivery and computer software that help in the body environment simulation, such as Gastroplus® software. The interest of this study is to prepare a gastroretentive film of metoclopramide HCl (MTC) that was followed by applying the in silico approach to estimate the in vivo prepared formulations. The films were prepared from HPMC E5 and sodium alginate polymers as primary polymers with the aid of secondary polymers. The sodium alginate high proportions films showed instant and long floating duration reaching 24 h but with variable folding endurance. Moreover, sodium alginate films with their secondary polymers carbopol and HPMC E5 slowed the release of MTC. The floating and slow-release patterns assessed the gastroretentive properties of sodium alginate films and were further examined by a mucoadhesive study that guaranteed mucosal adhesion, and the film's FESEM images showed similar top morphology, but different side view structures. Last, the pharmacokinetic profile of selected films that approached the gastroretentive properties was in silico predicted depending on in vitro release study and floating duration employing the physiological-based pharmacokinetic model in Gastroplus® software. The model determines this prediction found successfully of intravenous and immediate oral release tablets (10 and 30 mg) of MTC. The simulation showed a high amount of MTC retained for long periods in the stomach to Sod.Alginate-3, Sod.Alginate-8, and Sod.Alginate-10 films (films of secondary polymers carbopol and HPMC E5) aid in reaching the optimum site of absorption jejunum 1 due to the slow MTC release.

Development of starch/chitosan expandable films as a gastroretentive carrier for ginger extract-loaded solid dispersion.

Gastroretentive expandable films were developed to provide controlled release of ginger extract (GE) for treatment of gastric diseases. The dosage form consisted of ginger extract solid dispersion (GE-SD) loaded in a starch/chitosan composite film, which was subsequently folded and inserted into a hard gelatin capsule. GE-SD was prepared by solvent evaporation using an optimum weight ratio of 1:1 for GE and PVP K30. Expandable films containing GE-SD were prepared by solvent casting combinations of chitosan and either rice-, glutinous rice - or pregelatinized maize starch with glycerin incorporated as a plasticizer. The optimized film formulation prepared from glutinous rice starch, exhibited tensile strength of 5.4 N/cm2 and high expansion in simulated gastric fluid (SGF), resulting in a 2.8-fold increase in area. The films resulted in sustained release of up to 90% of the content of 6-gingerol during 8 h exposure to SGF. Furthermore, the 6-gingerol released from the film displayed dose-dependent cytotoxic activity against AGS human gastric adenocarcinoma cells and anti-inflammatory activity by inhibiting the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells.

Process Optimization for the Continuous Production of a Gastroretentive Dosage Form Based on Melt Foaming.

Several drugs have poor oral bioavailability due to low or incomplete absorption which is affected by various effects as pH, motility of GI, and enzyme activity. The gastroretentive drug delivery systems are able to deal with these problems by prolonging the gastric residence time, while increasing the therapeutic efficacy of drugs. Previously, we developed a novel technology to foam hot and molten dispersions on atmospheric pressure by a batch-type in-house apparatus. Our aim was to upgrade this technology by a new continuous lab-scale apparatus and confirm that our formulations are gastroretentive. At first, we designed and built the apparatus and continuous production was optimized using a Box-Behnken experimental design. Then, we formulated barium sulfate-loaded samples with the optimal production parameters, which was suitable for in vivo imaging analysis. In vitro study proved the low density, namely 507 mg/cm3, and the microCT record showed high porosity with 40 µm average size of bubbles in the molten suspension. The BaSO4-loaded samples showed hard structure at room temperature and during the wetting test, the complete wetting was detected after 120 min. During the in vivo study, the X-ray taken showed the retention of the formulation in the rat stomach after 2 h. We can conclude that with our device low-density floating formulations were prepared with prolonged gastric residence time. This study provides a promising platform for marketed active ingredients with low bioavailability.

Development and Optimization of Microballoons Assisted Floating Tablets of Baclofen.

The objective of the present study was to develop microballoons aided gastro-retentive floating tablets of baclofen, a skeletal muscle relaxant with a low elimination half-life of ~ 3.5 h. Baclofen floating tablet was prepared to offer convenience by designing a tablet that would float in the stomach for a prolonged period and allow controlled drug release to enable once-a-day administration. Ethylcellulose microballoons (ECMBs) prepared by pseudo emulsion solvent diffusion method were employed as floating aid. The ECMBs were spherical with a size of 446.71 µm and a circularity index of 0.995. Buoyancy of 98.90 percent and good flowability reflected by an angle of repose of 23° suggested the feasibility of preparing floating tablets by direct compression. Directly compressed baclofen floating tablets comprised ECMBs, HPMC-K15M, and hydroxyl ethylcellulose as independent variables in the Box-Behnken design, however, performance characteristics of tablets such as in vitro drug release, floating lag time, and swelling index were selected as the dependent variables. Among the variables, ECMBs played a critical role in ensuring buoyancy. However, HPMC-K15M significantly influenced in vitro drug release. The optimized batch displayed Hickson-Crowell kinetics and exhibited a similar drug release profile as a marketed once-a-day formulation (f2, 91.03). Furthermore, optimized tablets showed a swelling index of > 300, floating lag time < 3 s, and total floating time > 24 h. Microballoons assisted floating tablets exhibited great promise for assured gastric retention of tablets.

Assessment of the effect of polymers combination and effervescent component on the drug release of swellable gastro-floating tablet formulation through compartmental modeling-based approach.

The aim of this research was to assess the effect of polymer blend and effervescent components on the floating and swelling behaviors of swellable gastro-floating formulation as well as the drug release through a compartmental modeling analysis. Swellable gastro-floating formulation of freely water-soluble drug, metformin HCl as a drug model, was formulated and developed using D-optimal design. Polymer combination between interpolymer complex (IPC) (poly-vinyl acetate-copolymer methacrylate) and hydroxy propyl methyl cellulose (HPMC), and effervescent components were studied and optimized in this work. Several factors affecting the drug release behavior were determined e.g. swelling behavior, erosion behavior, and floating behavior were studied as well as the drug release through compartmental modeling analysis. The results revealed that the hydrophilic polymer was responsible for gas entrapment formed from effervescent reaction, meanwhile IPC contributed on maintaining the swollen matrix integrity through intermolecular polymer interaction. In addition, effervescent components played fundamental role in the formation of porous system as well as inducing burst release effect. Compartmental modeling provided different outlook about the drug release. Presence of IPC at a high proportion (10-15%) of the polymer blend modulated the changes of pattern of the drug release kinetics and mechanism. Finally, compartmental modeling-based approach was more adequate to describe the drug release kinetics and mechanism compared to the monophasic equation model correlating with process understanding of the drug release from swellable gastro-floating formulation.

Alfuzosin hydrochloride-loaded low-density gastroretentive sponges: development, in vitro characterization and gastroretentive monitoring in healthy volunteers via MRI.

The current work aimed to develop low-density gastroretentive sponges loaded with alfuzosin HCl (ALF) to sustain the rate of drug release, improve its oral bioavailability and deliver it to the main site of absorption. Sponges were developed, according to a 23 full factorial design, by compression of the lyophilized ALF-loaded hydroxypropylmethylcellulose (HPMC) or chitosan (CH) solutions. The influences of the polymer type, grade and concentration on the appearance, topography, porosity, density, in vitro ALF release, floating behavior, swelling, erosion, and mucoadhesive potential of the developed sponges were explored. Based on the desirability value, the best achieved system was selected. The gastroretentive potential of this system was evaluated in healthy male volunteers via MRI. Soft and flexible sponges were developed. They were characterized with interconnecting pores and channels and had excellent floating properties with respect to floating lag time and duration. Compared to HPMC-based sponges, CH-based ones exhibited higher porosity, larger pore diameters, lower bulk densities, higher drug release rates, larger swelling ratios, faster erosion rates and better mucoadhesive properties. MRI of magnetite-loaded best-achieved CH-based system (F8) ascertained the development of a promising gastroretentive system; exhibiting a gastric residence period of at least 5 h.

Gastroretentive bilayer film for sustained release of atorvastatin calcium and immediate release of amlodipine besylate: pharmaceutical, pharmacokinetic evaluation, and IVIVC.

The present study was aimed to optimize capsulated unfolding type gastroretentive bilayer film constituting immediate release (IR) layer of amlodipine besylate and sustained release (SR) layer of atorvastatin calcium. A three-factor, three-level Box-Behnken-design was used to optimize bilayer film with dual-release characteristics. The selected independent variables were HPMC-K3, Eudragit RSPO, and Carbopol 934P and the responses were floating duration, swelling index, and in vitro release from SR layer in 8 h. The films were also assessed for pharmacotechnical characteristics, release kinetics, DSC, FTIR, and SEM. The pharmacokinetics of the drugs from the optimized formulation was compared with the marketed formulation in rabbits. The capsulated accordion film unfolded and provided SR of atorvastatin for 8 h (96.76% ± 0.71) and IR of amlodipine within 25 min (98.07% ± 0.62) for the optimized formulation (F14). The swelling index and floating duration for the optimized formulation were 140.48 ± 0.57 and 8.53 ± 0.10 h, respectively. Results of pharmacokinetics showed that faster absorption of amlodipine and improved bioavailability (2.16-fold) of atorvastatin in blood was made available through bilayer film. In vitro-in vivo correlation was established using numerical deconvolution method. It can be concluded that the capsulated gastroretentive system provided site specific simultaneous SR of antihyperlidemic drug and IR of antihypertensive drug as single pill that has therapeutic potential to manage cardiovascular risk.

Artificial membranes in combination with selected natural oils for in vitro drug passive diffusion screening in Ussing type chamber apparatus applied to gastro-retentive systems.

This study aimed at developing an effective in vitro technique for the screening of drug passive diffusion utilising artificial membranes in combination with three selected oils (i.e. cognac, emu, and olive oil). Artificial membranes of varying chemical composition and characteristics have been investigated individually and in combination with the selected oils in terms of the passive diffusion of a fluorescent probe (i.e. Rhodamine 6G or R6G), in a diffusion apparatus as compared to excised pig intestinal tissues. In general, the permeation results showed that the rate and extent of R6G permeation were dependent on the membrane composition as well as the type of oil used. The apparent permeability coefficient (Papp) value for R6G across the cellulose nitrate membrane (0.197 × 10-7 ± 0.069 cm/s) was the closest to the Papp of R6G across the excised pig intestinal tissue (0.210 × 10-7 ± 0.080 cm/s). The cellulose acetate-nitrate mixture membrane impregnated with emu oil also produced a Papp value (0.191 × 10-7 ± 0.010 cm/s) that was relatively close to that of R6G across the excised pig intestinal tissue. The delivery of R6G from gastro-retentive matrix type tablets correlated with the release of R6G from the gastro-retentive tablets.

Development and Characterization of PCL Electrospun Membrane-Coated Bletilla striata Polysaccharide-Based Gastroretentive Drug Delivery System.

The purpose of this study was to investigate the potential of Bletilla striata polysaccharide (BSP, a natural glucomannan material) for the development of a gastroretentive drug delivery system for the first time. Novel BSP-based porous wafer was prepared for levofloxacin hydrochloride (LFH) delivery by combining floating, swelling, and mucoadhesion mechanisms. The influences of BSP and ethyl cellulose (EC) on drug release and mucoadhesive strength were studied by 32 factorial design. The optimized matrix was coated with polycaprolactone (PCL) electrospun membrane by electrospinning and heat treatment technology. The optimized formula (F6, coated) exhibited Q4 h of 41.20 ± 1.90%, Q8 h of 76.49 ± 1.69%, and mucoadhesive strength of 86.11 ± 1.33 gf, and its drug release profile most closely resembled the Korsmeyer-Peppas model with anomalous diffusion driving mechanism. F6 (coated) also presented excellent buoyancy, preferred swelling characteristic due to the porous structure formed by freeze-drying. Meanwhile, the internal morphology, physical state, drug-excipient compatibility, and thermal behavior were recorded. The negligible cytotoxicity of F6 (coated) was observed in human gastric epithelial cell cultures. In the in vitro antimicrobial experiment, the prepared wafer exhibited obvious bacterial inhibition zone, and due to its longer gastric retention, the wafer also performed a more effective Helicobacter pylori clearance than free LFH in vivo. Graphical abstract.

Linseed hydrogel based floating drug delivery system for fluoroquinolone antibiotics: Design, in vitro drug release and in vivo real-time floating detection.

Herein, we designed a novel gastroretentive drug delivery system as floating matrix tablets based on a polysaccharide material from linseeds (Linum usitatissimum L.) for fluoroquinolone antibiotics. A number of formulations were designed with a combination of linseed hydrogel (LSH) and different excipients to obtain a desired sustained release profile of moxifloxacin. The drug release study was performed basically at pH 1.2. However, the tablet may pass through the stomach to intestine due to certain reasons then it also offered sustained drug release at intestinal pH 4.5, 6.8 and 7.4, as well. Results indicated that sustained moxifloxacin release was directly proportional to the concentration of LSH and the release of drug followed non-Fickian diffusion. SEM of the tablets indicated porous nature of LSH with elongated channels which contributed to the swelling of the tablet and then facilitated the discharge of moxifloxacin from the core of the tablet. In vivo X-ray study was performed to assess disintegration and real-time floating of tablet that confirmed its presence for 6 h in the stomach. These findings indicated that LSH can be used to develop novel gastroretentive sustained release drug delivery systems with the double advantage of sustained drug release at all pH of GIT.