Simulated Small Intestinal Fluid Research Articles

In vitro simulated saliva, gastric, and intestinal digestion followed by faecal fermentation reveals a potential modulatory activity of Epimedium on human gut microbiota

Herba Epimedii, known for its rich array of bioactive ingredients and widespread use in ethnopharmacological practices, still lacks a comprehensive understanding of its gastrointestinal biotransformation. In this study, we qualitatively explored the dynamic changes in Epimedium sagittatum components during in vitro simulated digestions, with a quantitative focus on its five major flavonoids. Notably, significant metabolism of E. sagittatum constituents occurred in the simulated small intestinal fluid and colonic fermentation stages, yielding various low molecular weight metabolites. Flavonoids like kaempferol glycosides were fully metabolized in the simulated intestinal fluid, while hyperoside digestion occurred during simulated colon digestion. Colonic fermentation led to the production of two known bioactive isoflavones, genistein, and daidzein. The content and bioaccessibility of the five major epimedium flavonoids—icariin, epimedin A, epimedin B, epimedin C, and baohuoside I—significantly increased after intestinal digestion. During colon fermentation, these components gradually decreased but remained incompletely metabolized after 72 h. Faecal samples after E. sagittatum fermentation exhibited shift towards dominance by Lactobacillus (Firmicutes), Bifidobacterium (Actinobacteria), Streptococcus (Firmicutes), and Dialister (Firmicutes). These findings enhance our comprehension of diverse stages of Herba Epimedii constituents in the gut, suggesting that the primary constituents become bioaccessible in the colon, where new bioactive compounds may emerge.

Digestive characteristics of extracellular polysaccharide from Lactiplantibacillus plantarum T1 and its regulation of intestinal microbiota

This study assessed the potential prebiotic characteristics of the previously reported Lactiplantibacillus plantarum extracellular polysaccharide (EPS-T1) with immunological activity. EPS-T1 was a novel heteropolysaccharide composed of glucose and galactose (1.00:1.21), with a molecular weight of 1.41 × 106 Da. The monosaccharide composition, molecular weight, fourier transform infrared, and 1H NMR analysis showed that EPS-T1 was well tolerated in the simulated oral cavity, gastric fluid, and small intestinal fluid environments, and was not easily degraded. Meanwhile, EPS-T1 could effectively be used as a carbon source to promote the growth of beneficial Lactobacillus species (Lactobacillus delbrueckii ssp. Bulgaricus, Streptococcus thermophilus, Lacticaseibacillus rhamnose GG, Lactiplantibacillus plantarum, Lacticaseibacillus paracasei and Lactobacillus reuteri). After 24 h of fecal fermentation, EPS-T1(5 mg/mL) effectively reduced the relative abundance of harmful bacteria such as the Escherichia-Shigella, Citrobacter, Fusobacterium, Parasutterella, and Lachnoclostridium. While, the level content of beneficial flora (Bacteroides, Blautia, Phascolarctobacterium, Bifidobacterium, Parabacteroides, and Subdoligranulum) were significantly increased. In addition, EPS-T1 was able to significantly promote the enrichment of short-chain fatty acids such as acetic acid, propionic acid and butyric acid. These results provide some basis for the functional application of EPS-T1 as a potential prebiotic.

Advancing oral delivery of biologics: Machine learning predicts peptide stability in the gastrointestinal tract

The oral delivery of peptide therapeutics could facilitate precision treatment of numerous gastrointestinal (GI) and systemic diseases with simple administration for patients. However, the vast majority of licensed peptide drugs are currently administered parenterally due to prohibitive peptide instability in the GI tract. As such, the development of GI-stable peptides is receiving considerable investment. This study provides researchers with the first tool to predict the GI stability of peptide therapeutics based solely on the amino acid sequence. Both unsupervised and supervised machine learning techniques were trained on literature-extracted data describing peptide stability in simulated gastric and small intestinal fluid (SGF and SIF). Based on 109 peptide incubations, classification models for SGF and SIF were developed. The best models utilized k-Nearest Neighbor (for SGF) and XGBoost (for SIF) algorithms, with accuracies of 75.1% (SGF) and 69.3% (SIF), and f1 scores of 84.5% (SGF) and 73.4% (SIF) under 5-fold cross-validation. Feature importance analysis demonstrated that peptides’ lipophilicity, rigidity, and size were key determinants of stability. These models are now available to those working on the development of oral peptide therapeutics.

Construction and sustained release of konjac glucomannan/naringin composite gel spheres.

To improve the bioavailability of active substances and reduce the toxic and side effects on the human body, natural biological macromolecules are used to load active substances and control their release speed in different environments of the human body. In this study, mesoporous silica (MSN) was combined with konjac glucomannan (KGM) and sodium alginate (AC) to prepare pH-sensitive konjac glucomannan/sodium alginate-mesoporous silica loaded naringin gel spheres (KS/MSN). On this basis, the structure, morphology, and release properties of the composite gel spheres were characterized. The results showed that the cumulative release rates of both simulated gastric fluid (SGF) and Simulated colonic fluid (SCF) were lower than that of simulated small intestinal fluid (SIF), which indicated that the prepared composite gel spheres were pH-sensitive to SIF and obtained the best release rate of about 70% under SIF environment. The pH-sensitive konjac glucomannan/sodium alginate composite gel spheres (KGM/SA) were prepared by combining inorganic nano-materials mesoporous silica (MSN) with natural macromolecular polysaccharides konjac glucomannan (KGM) and sodium alginate (SA) and characterized. The results showed that there was a process of ionic crosslinking and entanglement between konjac glucomannan (KGM) and sodium alginate (SA). Naringin (NG) and mesoporous silica (MSN) were successfully compounded and had good compatibility. The gel microstructure diagram showed that the addition of MSN improved the gel properties of KGM, and KGM and SA gel spheres (KGM/SA) had good compatibility with mesoporous silica/naringenin nanoparticles (NG/MSN). The study of the simulated digestive environment of the gastrointestinal release medium showed that Konjac glucomannan/sodium alginate-mesoporous silica loaded naringin gel spheres (KS/NM) composite gel spheres had the best slow-release effect and the highest final-release completion degree in SIF. The release of NG from KS/NM composite gel spheres showed a slow upward trend. The results showed that KS/NM composite gel spheres were pH-sensitive. The KS/NM composite gel spheres showed obvious pH sensitivity to the release of NG, and the gel spheres had a good sustained release effect on NG.

Predicting the metabolizable energy and metabolizability of gross energy of conventional feedstuffs for Muscovy duck using in vitro digestion method.

In total, two experiments were conducted to evaluate the effectiveness of an in vitro digestion method for predicting the metabolizable energy (ME) and metabolizability of gross energy (ME/GE) values using in vitro digestible energy (IVDE) and the digestibility of gross energy (IVDE/GE) content, respectively, of conventional feedstuffs for Muscovy ducks. In experiment 1, the apparent metabolizable energy (AME), true metabolizable energy (TME), AME/GE, and TME/GE of eight-grain feedstuff samples (two corn samples, three sorghum samples, and three barley samples) and eight protein feedstuff samples (two soybean meal samples, three cottonseed meal samples, and three rapeseed meal samples) were determined by the tube-feeding method with six different ducks for each sample. In experiment 2, a computer-controlled simulated digestion system (CCSDS) contain simulated digestive fluid was used to determine the enzymatic hydrolysis energy value of feedstuffs, which was defined as IVDE in our study. The simulated gastric fluid containing pepsin and simulated small intestinal fluid containing amylase, trypsin, and chymotrypsin for the in vitro gastric and intestinal digestion, respectively. The IVDE and in vitro digestibility of GE (IVDE/GE) of 16 feedstuff samples were determined using the CCSDS with five replicates per sample. The results showed that the IVDE and IVDE/GE were positively correlated with ME and ME/GE of feedstuffs, respectively. The coefficient of determination of eight regression models in predicting ME (grain feedstuffs: AME = 1.050 × IVDE- 0.9293, TME = 1.032 × IVDE + 0.6478; protein feedstuffs: AME = 1.331 × IVDE- 6.685, TME = 1.269 × IVDE-3.490) and ME/GE (grain feedstuffs: AME/GE = 1.069 × IVDE/GE- 6.516, TME/GE = 1.068 × IVDE/GE + 0.7764; protein feedstuffs: AME/GE = 1.093 × IVDE/GE -19.21, TME/GE = 1.196 × IVDE/GE - 13.25) of feedstuffs for Muscovy ducks ranged from 0.8610 to 0.9921. The accuracy of the regression model was acceptable as the difference between measured and predicted ME and ME/GE values was less than 0.45 MJ/kg (100 kcal/kg) and 2.62% for 14 of the 16 feed samples, respectively. In conclusion, the in vitro digestion method can be used to predict the ME and ME/GE of conventional feedstuffs for Muscovy ducks with acceptable accuracy.

Assessment of the Intestinal Absorption of Higher Olefins by the Everted Gut Sac Model in Combination with In Silico New Approach Methodologies.

To reduce the number of animals and studies needed to fulfill the information requirements as required by Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (EC no. 1907/2006), a read-across approach was used to support approximately 30 higher olefins. This study aimed to assess the absorption potential of higher olefins through the gut wall as the experimentally determined bioavailability which would strengthen the read-across hypothesis and justification, reducing the need for toxicity studies on all of the higher olefins. The absorption potential of a series of higher olefins (carbon range from 6 to 28, with five configurations of the double bond) was determined in the in vitro everted rat small intestinal sac model and subsequently ranked. In addition, in silico approaches were applied to predict the reactivity, lipophilicity, and permeability of higher olefins. In the in vitro model, everted sacs were incubated in “fed-state simulated small intestinal fluid” saturated with individual higher olefins. The sac contents were then collected, extracted, and analyzed for olefin content using gas chromatography with a flame ionization detector. The C6 to C10 molecules were readily absorbed into the intestinal sacs. Marked inter-compound differences were observed, with the amount of absorption generally decreasing with the increase in carbon number. Higher olefins with ≥C14 carbons were either not absorbed or very poorly absorbed. In the reactivity simulation study, the reactivity is well described by the position of the double bond rather than the number of carbon atoms. In the lipophilicity and permeability analysis, both parameter descriptors depend mainly on the number of carbon atoms and less on the position of the double bond. In conclusion, these new approach methodologies provide supporting information on any trends or breakpoints in intestinal uptake and a hazard matrix based on carbon number and position of the double bond. This matrix will further assist in the selection of substances for inclusion in the mammalian toxicity testing programme.

Smart controlled release of acarbose from glucose‐sensitive hydrogels comprising covalently modified carboxylated pullulan and concanavalin A

AbstractA hydrogel comprising covalently modified carboxylated pullulan and concanavalin A (CPUL‐ConA) was prepared with glucose‐sensitivity in a simulated small intestinal fluid containing glucose. The acarbose‐encapsulated CPUL‐ConA (Acar/CPUL‐ConA) hydrogel, with an acarbose encapsulation ratio of 0.63, was prepared by immersing the dried CPUL‐ConA hydrogel in an acarbose/PBS (pH 7.2) solution. In the simulated gastric fluid, less than 20% acarbose was released from the Acar/CPUL‐ConA hydrogel, which could be beneficial to protecting the stomach. In contrast, more than 80% acarbose was smartly controlled released from the Acar/CPUL‐ConA hydrogel in the simulated small intestine fluid containing glucose. Scanning electron microscopy provided further evidence of the smart release of acarbose from the Acar/CPUL‐ConA hydrogel in simulated gastrointestinal fluids, which is advantageous to inhibiting α‐glucosidase activity and subsequently reducing the postprandial blood glucose levels, as well as helpful for reducing the gastrointestinal dysfunction of acarbose. Rheological analysis indicated that the Acar/CPUL‐ConA hydrogel showed characteristics of chemical crosslinked hydrogels. There was no obvious shear thinning behavior, suggesting that the Acar/CPUL‐ConA hydrogel could be stable under gastric and intestinal peristalsis. Therefore, the Acar/CPUL‐ConA hydrogel is anticipated to improve the therapeutic efficacy of postprandial hyperglycemia and type 2 diabetes.

Comparative study on the stability/intestinal absorption kinetics of 2,3,5,4′-tetrahydroxy-stilbene-2-O-β-D-glucoside derived from Polygoni Multiflori Radix and its herb pairs

The 2,3,5,4’-tetrahydroxy-stilbene-2-O-β-D-glucoside (THSG) is a main active ingredient of Polygoni Multiflori Radix (PMR). In this study, THSG was found to be a differential chemical composition between PMR and its compatible herb pairs through chemometrics techniques. The effects of the herb pairs Codonopsis Radix-PMR, Astragali Radix-PMR, and Ophiopogonis Radix (OR)-PMR on the stability and absorption behavior of THSG were investigated by simulating the digestive environment in vitro and using an everted gut sac model. The results indicated that the compatible pairs were able to significantly increase the stability of THSG in the gastrointestinal tract and delay the absorption of THSG in the small intestine. OR had the most obvious influence on THSG as the t0.9 values of THSG increased by 14.74- and 6.68-fold in simulated gastric juice and small intestinal fluid, and the apparent permeability coefficient of THSG were 2.07- and 1.97-fold lower for OR-PMR in the ileum and duodenum, respectively. Thus, the compatibility could potentially be used to change the biopharmaceutical properties of THSG. Moreover, the present study established a research method for describing the compatibilities of traditional Chinese medicine based on stability-intestinal absorption, which may provide important reference values for the compatibilities of traditional Chinese medicine.

Octenyl-succinylated inulin for the encapsulation and release of hydrophobic compounds

Octenyl-succinylated inulins (OSA-inulin) were synthesized in aqueous solutions using inulin with varying degrees of polymerization (DP). They were characterized using 1H NMR and FTIR and their degrees of substitution were determined. All the samples formed micellar aggregates in aqueous solution above a critical aggregation concentration (CAC) and solubilized beta-carotene. The amount of beta carotene solubilized within the micelles ranged from 12 to 25 mg/g of OSA-inulin and depended on the inulin molar mass. Dynamic light scattering showed that the aggregates, with and without dissolved beta-carotene, were ∼10–15 nm in size and this was confirmed by Transmission Electron Microscopy which also indicated that the micelles had a globular shape. OSA-inulin particles containing encapsulated beta-carotene were produced by freeze-drying. The encapsulated beta-carotene was not released from the freeze-dried particles when introduced into simulated gastric fluid at pH 2.5 but was readily released in simulated small intestinal fluid at pH 7. The results demonstrate the potential application of OSA-inulin in the encapsulation, dissolution and targeted delivery of hydrophobic drug molecules for nutraceutical, pharmaceutical and medical applications.

An Enteric-Coated Polyelectrolyte Nanocomplex Delivers Insulin in Rat Intestinal Instillations when Combined with a Permeation Enhancer.

The use of nanocarriers is being researched to achieve oral peptide delivery. Insulin-associated anionic polyelectrolyte nanoparticle complexes (PECs) were formed that comprised hyaluronic acid and chitosan in an optimum mass mixing ratio of 5:1 (MR 5), followed by coating with a pH-dependent polymer. Free insulin was separated from PECs by size exclusion chromatography and then measured by HPLC. The association efficiency of insulin in PECs was >95% and the loading was ~83 µg/mg particles. Dynamic light scattering and nanoparticle tracking analysis of PECs revealed low polydispersity, a negative zeta potential range of −40 to −50 mV, and a diameter range of 95–200 nm. Dissolution studies in simulated small intestinal fluid (FaSSIF-V2) revealed that the PECs were colloidally stable. PECs that were coated with Eudragit® L-100 delayed insulin release in FaSSIF-V2 and protected insulin against pancreatin attack more than uncoated PECs. Uncoated anionic PECs interacted weakly with mucin in vitro and were non-cytotoxic to Caco-2 cells. The coated and uncoated PECs, both concentrated further by ultrafiltration, permitted dosing of 50 IU/kg in rat jejunal instillations, but they failed to reduce plasma glucose or deliver insulin to the blood. When ad-mixed with the permeation enhancer (PE), sucrose laurate (100 mM), the physicochemical parameters of coated PECs were relatively unchanged, however blood glucose was reduced by 70%. In conclusion, the use of a PE allowed for the PEC-released bioactive insulin to permeate the jejunum. This has implications for the design of orally delivered particles that can release the payload when formulated with enhancers.

Validation of in vitro digestion using simulated small intestinal fluid with specific digestive activity to predict the metabolizable energy of feed ingredients for duck

Two experiments were conducted to validate a method to prepare simulated small intestinal fluid (SSIF) for in vitro digestion in ducks. Experiment 1 compared the in vitro digestible energy (IVDE) of SSIF to endogenous small intestinal fluid (ESIF) on four feeds. The ESIF 1 or 2 obtained from two groups of jejunal cannulated ducks offered diet 1 (3,050kcal/kg of ME and 19.95% of CP) or 2 (2,801kcal/kg of ME and 14.90% of CP) was purified into raw enzyme power (REP) 1 or 2. SSIF 1 to 3 or 4 to 6 were prepared to mimic ESIF 1 or 2, respectively. The enzyme sources were REP 1 for SSIF 1 and 4, REP 2 for SSIF 2 and 5 or reagent enzymes for SSIF 3 and 6, respectively. The IVDE of each feed was determined with SSIF or ESIF. Experiment 2 was to validate whether REP 1 was more effective than only reagent enzymes to prepare SSIF. Ten feeds were determined with pepsin following SSIF 1 or 3 for IVDE 1 or 2, respectively. The accuracy of prediction model of true metabolizable energy (TME) from IVDE 1 or 2 was evaluated to validate the efficacy of SSIF. In experiment 1, higher activities of amylase, trypsin and chymotrypsin were observed in ESIF 1 than ESIF 2 (P < 0.05). The IVDE determined with SSIF 1 and 2 or 3 and 4 were more comparable to that of ESIF 1 or 2 than determinations with SSIF 3 or 6. In experiment 2, the mean IVDE 1 or 2 was 97.22% or 96.23% relative to TME, respectively, and both were highly correlated with TME (P < 0.01; R2 ≥ 0.98). However, the residual SD of TME prediction model with IVDE 1 was less than that generated with IVDE 2 (55vs. 71kcal/kg). In conclusion, the IVDE determined with in vitro digestion of pepsin following SSIF prepared with REP can predict accurately TME of feed for ducks.

Structural characterization and biological fate of lactoferrin-loaded liposomes during simulated infant digestion.

Limited information is concerned on the structure changes of liposomal delivery system under infant conditions. Positively charged lactoferrin (LF)-loaded liposomes, with the entrapment efficiency (EE) of 52.3±6.3%, were prepared from soybean-derived phospholipids using a thin-layer dispersion method. The structure changes and digestibility of LF-loaded liposomes under infant conditions, including simulated gastric fluid (SGF) and simulated small intestinal fluid (SIF), were characterized in terms of the average particle size, zeta potential, turbidity, fourier transform infrared, transmission electron microscopy, lipolysis and protein hydrolysis. This study showed that the functional groups, favorable membrane structure and the EE of liposomes were slightly changed as a function of time when the liposome digested under SGF conditions. However, the intact bilayer structures were damaged and the EE of LF-loaded liposomes decreased to 28.5% after digestion in infant SIF. These results suggested that liposomal membrane could prevent the gastric degradation and the structure of liposomes was not completely destroyed with a low concentration of pancreatin and bile salts under infant conditions. Present study provided information on the insight into the characteristics of liposomes during infant gastrointestinal digestion, which was useful for the development of microcapsule systems in infant diet. © 2018 Society of Chemical Industry.

A novel polysaccharide gel bead enabled oral enzyme delivery with sustained release in small intestine

We report a novel oral delivery system based on sodium alginate/κ-carrageenan binary polysaccharide gel bead. β-galactase was selected as a model molecule to evaluate the capacity of the beads as delivery system. After enzyme encapsulation, the hydrogel beads were subsequently coated with κ-carrageenan (κ-CG) and ε-polylysine (ε-PL). Scanning electron microscope (SEM) images revealed the microstructural differences between the beads synthesized with and without ε-PL coating. Fourier transform infrared spectroscopy (FTIR) spectra further proofed the successful coating of ε-PL and κ-CG. Releasing studies showed that the enzyme releasing time is significantly prolonged by ε-PL coating. In vitro experiments showed that, the hydrogel beads synthesized with 0.6% ε-PL were stable and compact in the simulated gastric fluid environment with negligible swelling, which can protect the loaded enzyme effectively. More than 94.6% lactase activity can be retained after treated with simulated gastric fluid (pH 4) for 2 h. After transferred into simulated small intestinal fluid for 14 h (pH 7.4), as much as 89.6% of the enzyme can be released from the beads. It is worthy to note that the activity of the released enzyme retained 76.0% of total enzyme activity. These unique properties of the hydrogel beads enabled the effectively maintenance of enzyme bioactivity and thus enhanced the enzyme delivery and therapeutic efficiency. The reported delivery system is an ideal oral delivery system for bioactive food compounds, especially for compounds that are unstable in gastric environment.

Control of the gastrointestinal digestion of solid lipid nanoparticles using PEGylated emulsifiers

We prepared solid lipid nanoparticles (SLNs) with tristearin and various emulsifiers which had different chain length PEGs (10–100 times-repetition of ethylene glycol) to control their digestion fate in the gastrointestinal tract. Fabricated SLNs after acidic/high-ionic-strength media treatment were stable regardless of the ζ-potential (ZP) disappearance. Additionally, highly PEGylated SLNs successfully hindered the adsorption of both bile acid (BA) and lipase on the SLN surface, while lowly PEGylated SLNs interrupted that of only lipase. In simulated small intestinal fluid, lipolysis of highly PEGylated SLNs increased with decrease of the emulsifier density on the SLNs, whereas lipolysis of lowly PEGylated SLNs increased with decrease of the particle size. These results suggested that high PEGylation was more efficient than low PEGylation to hinder the lipolysis initiated from the competitive replacement of the SLN-covering emulsifiers with BAs. Consequently, the SLN digestion could be controlled by choosing the length and concentration of PEGylated emulsifiers.

Liquid-core alginate hydrogel beads loaded with functional compounds of radish by-products by reverse spherification: Optimization by response surface methodology

Liquid-core hydrogel beads (LHB) were formulated through reverse spherification, by sodium alginate and using calcium lactate (CL) to replace the common calcium source, calcium chloride. The effect of four independent variables: first gelation time (X1), CL concentration in first gelation (X2), secondary gelation time (X3), and CL concentration in secondary gelation (X4), on seven physical properties of LHB: diameter, hardness (Y1), loading efficiency (LE, Y2), release amount of total phenolic compounds (TP) in simulated gastric (Y3) and small intestinal (Y4) fluid, swelling capacity (Y5), and sphericity (Y6), were evaluated. Furthermore, a central composite design with response surface methodology was used for the optimization of LHB properties Y1–Y6, and the importance of the four independent variables to physical properties was analyzed. The diameter of LHB was in the range of 4.17–5.84mm. The optimal conditions of LHB formulation were first gelation time of 23.99min, 0.13M CL in the first gelation, secondary gelation time of 6.04min, and 0.058M CL in secondary gelation. The optimized formulation of LHB demonstrated 25.5N of hardness, 85.67% of LE and 27.38% of TP release in simulated gastric fluid with the small error-values (−2.47 to 2.21%).

Producing liquid-core hydrogel beads by reverse spherification: Effect of secondary gelation on physical properties and release characteristics

Burdock leaf contains abundant chlorogenic acid (CGA) and phenolic compounds and is a popular material for research. We used reverse spherification, where burdock leaf extracts mixed with calcium ion are dropped into sodium alginate solution to produce liquid-core hydrogel beads (LHB), and evaluated the effect of different calcium concentration in secondary gelation on the swelling capacity, hardness, microstructure, and release kinetics and mechanisms of LHB during thermal and simulated gastrointestinal fluid (in vitro) treatments. The LHB were prepared by 0, 0.5, and 1.0 g/100 mL CaCl2 in secondary gelation, and expressed as CA0, CA0.5, and CA1, respectively. As calcium concentration in secondary gelation increased, flake structure on the surface of LHB disappeared, and a rough, bumpy surface emerged. Furthermore, the stability of LHB increased, the change of swelling capacity and hardness decreased, the number of cavities on the surface of LHB and release rate of CGA during thermal and in vitro treatments decreased. The CGA release profile of CA0 conformed to zero-order kinetics model (R2 = 0.990–0.993) and CA0.5 and CA1 were conformed to Higuchi kinetics model (R2 = 0.899–0.980). The release exponent (n) of CA0 during thermal treatment ranged from 0.525 to 0.597, indicating the release mechanism was anomalous transport, and release mechanisms of CA0.5 and CA1 were Fickian diffusion (n = 0.229–0.373). CA1 exhibited the highest quality among the three conditions, but low release amount and rate of CGA in simulated small intestinal fluid needed improvement.

Surface Molecularly Imprinted Polymer of Chitosan Grafted Poly(methyl methacrylate) for 5-Fluorouracil and Controlled Release.

The molecular surface imprinted graft copolymer of chitosan with methyl methacrylate (MIP-CS-g-PMMA) were prepared by free radical polymerization with 5-fluorouracil (5-FU) as the template molecule using initiator of ammonium persulfate as adsorption system. MIPs were characterized by FTIR, X-ray diffraction, thermo-gravimetric analysis, 1H NMR and SEM. The mechanism of graft copolymerization and factors affected graft reaction were studied in details, and the optimum reaction conditions (to the highest %G and %E as the standard) were obtained at [MMA] 1.2 mol/L, [Chitosan] 16.67 mol/L, [initiator] 0.0062 mol/L, temperature 60 °C and reaction time 7 h. MIPs exhibited high recognition selectivity and excellent combining affinity to template molecular. The in vitro release of the 5-FU was highly pH-dependent and time delayed. The release behavior showed that the drugs did not release in simulated gastric fluid (pH = 1.0), and the drug release was small in the simulated small intestinal fluid (pH = 6.8), and drug abrupt release will be produced in the simulated colon fluid (pH = 7.4), indicating excellent colon-specific drug delivery behavior.

Dissolution Profile of Mefenamic Acid Solid Dosage Forms in Two Compendial and Biorelevant (FaSSIF) Media.

Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID) that is widely used for the treatment of mild-to-moderate pain. Mefenamic acid belongs to the Biopharmaceutical Classification System (BCS) class II drug which has lower water solubility but high permeability. There are two different compendial methods available for dissolution tests of mefenamic acid solid dosage forms, i.e. methods of United States Pharmacopeia 37 (USP) and Pharmacopoeia of the People’s Republic of China 2010 (PPRC). Indonesian Pharmacopeia V ed. (FI) adopted the USP method. On the other hand, many researches focused on the use of a ‘biorelevant’ medium to develop the dissolution test method. The aim of this research was to study the dissolution profile of mefenamic acid from its solid dosage forms (caplet and capsule) available in the Indonesian market with three different dissolution medium: USP, PPRC, and biorelevant fasted simulated small intestinal fluid (FaSSIF) media. The tested products consisted of the innovator’s product (available only in caplet dosage form, FN caplet) and generic products (available as caplet and capsule). The dissolution test of the drug products in all dissolution media was performed in 900 mL of medium using apparatus II (paddle) at a temperature of 37°C and rotation speed of 75 rpm, except for the capsule product and for USP medium, both of which tests were done using apparatus I (basket) with rotation speed of 100 rpm. The solubility test of mefenamic acid was carried out in all media at temperature of 37°C. The result obtained from the solubility test showed that the the highest solubility of mefenamic acid was obtained in USP medium (approximately 2 mg/mL), followed by PPRC medium (about 0.5 mg/mL), and FaSSIF medium (approximately 0.06 mg/ml). In the dissolution test, percentage of drug dissolved in in the USP and PPRC media after 45 min for all products reached more than 75%, except for the PN caplet in USP medium which reached only about 44%. Meanwhile, in the biorelevant medium, the percentage of drug dissolved for all products did not exceed 16%. In all dissolution media, the capsule dosage form achieved the highest dissolution rate.

Structural and release properties of amylose inclusion complexes with ibuprofen

Complexes of amylose (AS) with ibuprofen (IBF) were prepared by the acidification method to yield V-type structure with different IBF-AS ratios. Among the ratios being tested, the IBF-AS ratio of 1/10 gave the highest yields (52.6%, w/w) and IBF content in the complex (14.1%, w/w). The XRD and 13C CP/MAS NMR spectra indicated that the AS and IBF formed the V-amylose complexes. The DSC and FT-IR analysis further testified the formation of the AS-IBF inclusion complexes. These complexes are stable in simulated gastric fluid (pH 1.2), with <5.5% of the complexed IBF. All complexes show sustained release characteristics in simulated small intestinal fluid (pH 7.2). It is evident that the ibuprofen cumulative release of complexes increased with the increase of IBF-AS ratios. Therefore, the AS-IBF complexes can be used as intestinally targeted and slow releasing drugs based on the action of enzymatic hydrolysis of AS.

Preparation and Characterization of Metronidazole-Surface Imprinted Microspheres MIP-PSSS/CPVA for Colon-Specific Drug Delivery System

In this paper, the use of molecular surface imprinted polymers (MIPs) in designing colon-specific drug delivery systems was investigated. MIPs were prepared on crosslinked polyvinyl alcohol microspheres (CPVA) with sodium 4-styrene sulfonate (SSS) as functional monomer, Metronidazole (MTZ) as template and N,N’-Methylene bisacrylamide (MBA) as crosslinking agent by utilizing cerium salt-hydroxyl group redox initiation system, obtaining MTZ molecular surface imprinted microspheres MIP-PSSS/CPVA. The MIP-PSSS/CPVA microspheres were further characterized by scanning electron microscope and batch binding method. Because there is strong electrostatic interactions between MTZ and monomer SSS, the MTZ molecular surface imprinting is quite successful, and the imprinted microspheres MIP-PSSS/CPVA possess high recognition selectivity and excellent combining affinity. The experimental results show that at pH 1, the MIP-PSSS/CPVA microspheres exhibit very strong binding ability for MTZ, and the binding capacity reaches up to 115 mg/g. The in vitro release of the MTZ-loaded MIP-PSSS/CPVA is highly pH-dependent and time-delayed. The release behavior shows that the drugs do not release in simulated gastric fluid (pH = 1), the drug release is small while in the simulated small intestinal fluid (pH = 6.8), an abrupt release will be firstly produced and then drug release is sustained and slowed in the simulated colon fluid (pH = 7.4), displaying excellent colon-specific drug delivery behavior.