Gastrointestinal Membrane Research Articles

Ex vivo permeability study of poorly soluble drugs across gastrointestinal membranes: acceptor compartment media composition

Ex vivo drug permeability testing across gastrointestinal (GI) membranes is crucial in drug discovery and oral drug delivery. It is a reliable method for drugs with good solubility, but it poses challenges for poorly soluble drugs, which are common in development pipelines today. Although enabling formulations increase the apparent solubility in the GI compartment (dissolution vessel or permeation chamber's donor compartment), maintaining solubilized drug in the acceptor compartment during ex vivo testing remains largely unresolved. This review compiles and critically evaluates the diverse compositions of acceptor media used in ex vivo permeability studies for poorly soluble drugs, highlighting this significant yet underexplored aspect of pharmaceutical science. An algorithm is proposed for selecting solubility-enhancing additives for the acceptor media in ex vivo permeability studies of poorly soluble drugs.

Natural deep eutectic solvents: A paradigm of stability and permeability in the design of new ingredients

Ascorbic Acid (AA) is a crucial component in the food industry, serving as both a quality and safety criterion. It is used to fortify foods due to its significant role in human health, acting as an antioxidant. Its benefits extend to both product quality and consumer health in the food and cosmetic industry. Due to their physicochemical properties, Natural Deep Eutectic Solvents (NADES) have the potential to be used for the extraction and stabilization of bioactive compounds. The objective of this study is to characterize various NADES, simulate the solubility of AA, evaluate the antioxidant and protective capacity of NADES, and investigate the permeability of this vitamin through the skin and gastrointestinal membrane. Antioxidant capacity was measured using three methods: TEAC, DPPH, and ORAC. The solubility of AA in NADES systems was simulated using the COSMOTherm software. The degradation of AA was monitored by HPLC/UV–Vis for 30 days at two different storage temperatures. Additionally, the membrane solubility was measured using the PAMPA method in both skin and gastrointestinal. The results indicate that organic acid-based NADES are more polar than sugar and polyalcohol-based NADES. The solubility prediction shows that reduced ln(γ) in Choline chloride-based NADES results in low AA solubility, which positively correlates with higher pH values. AA degradation increased at lower pH, and its half-life time was longer at 4 °C, being the best choline chloride (ChChl):xylose. Moreover, betaine:malic acid, ChChl:tartaric acid, and ChChl:lactic acid gave worse stabilizing results than control. According to the PAMPA study, AA in lactic acid:glucose had the highest Pe (permeability coefficient) for both gastrointestinal (Log Pe: −4.99) and skin (Log Pe: −4.78). Malic acid:glucose, on the other hand, had the lowest LogPe value (−6.9). In this study, some NADES can play a protective role in the preservation of ascorbic acid. This statement could be extended to other bioactive compounds found in NADES extracts that may be impacted by oxidative processes. Moreover, not all NADES stabilized equally AA. These findings could be applied to the formulation of ascorbic acid-containing drugs, cosmetics, and food products.

Intestinal Membrane Function in Inflammatory Bowel Disease.

Inflammatory bowel disease is a set of chronic inflammatory diseases that mainly develop in the gastrointestinal mucosa, including ulcerative colitis and Crohn's disease. Gastrointestinal membrane permeability is an important factor influencing the pharmacological effects of pharmaceuticals administered orally for treating inflammatory bowel disease and other diseases. Understanding the presence or absence of changes in pharmacokinetic properties under a disease state facilitates effective pharmacotherapy. In this paper, we reviewed the gastrointestinal membrane function in ulcerative colitis and Crohn's disease from the perspective of in vitro membrane permeability and electrophysiological parameters. Information on in vivo permeability in humans is summarized. We also overviewed the inflammatory bowel disease research using gut-on-a-chip, in which some advances have recently been achieved. It is expected that these findings will be exploited for the development of therapeutic drugs for inflammatory bowel disease and the optimization of treatment options and regimens.

Goal-directed fluid therapy compared to liberal fluid therapy in patients subjected to colorectal surgery

ABSTRACT Background The best technique to manage intraoperative fluids during colorectal surgery has never been universally agreed upon. Key organ function is hampered by excessive intraoperative fluid administration: It lengthens and raises the expense of hospitalization by increasing the risk of heart failure that goes along with it, causing gastrointestinal membrane edema, and impeding the recovery of gastrointestinal functions. Aim and objectives Thestudy’s objective was to evaluate the impacts of goal-directed fluid therapy (GDFT) and liberal fluid therapy (LFT) using cardiometry in candidates with colorectal abnormalities. Subjects and methods 100 patients were allocated into two equal groups in a random pattern for this prospective, randomized, controlled trial at the Mansoura oncology center; GDFT group) 50 patients): by using stroke volume optimization and the LFT group (50 patients): by using the traditional technique of fluid administration. Results Crystalloid and total fluids were significantly lower among GDFTgroup compared to LFT group. Both lactate and creatinine levels were slightly higher among the GDFT group than the LFT group but without a statistically significant difference. Postoperative complications were comparable between the studied groups. Conclusions However, GDFT needs lower total volume of fluids given to the patients it may not enhance patients’ postoperative outcomes after colorectal surgery compared to liberal fluid treatment. Moreover, both studied strategies did not affect organ perfusion, although serum lactate and serum creatinine were slightly higher with GDFT.

In vitro characterization of cadmium transport across the gastro-intestinal membrane of the fathead minnow (Pimephales promelas) in the presence and absence of microplastics

There is concern that microplastics can act as a vector for cadmium through adsorption and desorption of free-ionic cadmium. Little is known about the uptake of cadmium following ingestion of cadmium-microplastic complexes. This study used an in vitro gut sac technique to investigate the translocation of cadmium across the gut barrier of fathead minnows following the simulated ingestion of cadmium, microplastics, or their complexed mixture. Microplastics did not cross the gut membrane, nor did microplastics alter the rate of cadmium translocation, which was estimated to be 1.2 ± 0.04 ng Cd / hour. Less cadmium translocated when cadmium-microplastic complexes were injected than the equivalent dose of only cadmium, indicating that the presence of microplastics was protective of dietary cadmium uptake. This work highlights the importance of considering dietary uptake and the role of microplastics acting as a vector for cadmium in aquatic environments and stresses the need to understand how environmental (digestive or ambient) characteristics govern cadmium-microplastic interactions.

Safety and efficacy of substance-based medical devices: Design of an in vitro barrier effect test

This study aims to develop an in vitro barrier effect test over biomimetic membrane, which is useful to establish the film forming ability of a substance-based medical device (SB-MD). The method contemplates a multiparametric approach including: i) the measurement of the transmembrane passage of a molecular-like marker over a lipid-impregnated biomimetic membrane (simulating the skin and gastro-intestinal and buccal tissues) by using a static diffusion cell apparatus (Franz cell); and ii) the evaluation of the integrity of the membrane (colorimetric test). In the first step, a series of lipid-impregnated biomimetic membranes (simulating gastro-intestinal, buccal, and skin tissues) were implemented and their permeability performance validated using model drugs (caffeine and acyclovir) by referring to literature data. As a result, the apparent permeability (Papp) of caffeine over the biomimetic gastro-intestinal membrane (Papp = 30.5E-6 cm/s) was roughly comparable to the literature values obtained with Caco-2 cell line membrane (Papp = 30.8E-6 cm/s) and with the Franz cell method (Papp = 36.2E-6 cm/s). Acyclovir was shown to be a poorly permeable substance both in the literature and experimental data. Following this step, the permeability study was extended to both biomimetic buccal and skin (STRAT-M®) membranes: for caffeine, biomimetic gastro-intestinal membrane was the most permeable (Papp = 30.5E-6 cm/s), followed by the buccal (Papp = 18.2E-6 cm/s) then the skin (Papp = 0.5E-6 cm/s) biomimetic membranes. In a second part of the work, the barrier effect test was developed following a similar permeability-like approach. The protocol was designed with the idea of assessing the capacity of a certain product to prevent the passage of caffeine across the biomimetic membrane with respect to a negative and positive control. The untreated membrane was the negative control, while membrane covered with a Vaseline film was the positive. As a last step, the developed barrier effect protocol was applied to an experimental gel-like SB-MD under development for the treatment of aphthae (Aphthae gel, an invented trade name), herein used as a case study. Regarding the results, Aphthae gel reduced the caffeine passage by 60.3%, thus highlighting its effectiveness to form a protective film. Overall, these results provide important knowledge and may pave the way for the use—including for industrial applications—of these simple but effective biomimetic membranes for carrying out high throughput screening necessary to design safe and effective SB-MDs before proceeding further with clinical trials, as requested by the regulations.

Lactose hydrate can increase the transcellular permeability of β-naphthol in rat jejunum and ileum.

The unstirred water layer (UWL) is an integral part of the apical surface of mucosal epithelia and comprises mucins (MUC), for which there are many molecular species. Galectins, a family of β-galactoside-bindinglectins, form a lattice barrier on surface epithelial cells by interacting with MUC. Lactose inhibits the galectin-MUC interaction. Therefore, the present study investigated the galectin-MUC interaction in the mucosa of the gastrointestinal tract and its role in intestinal barrier functions. The effects of lactose hydrate (LH) on the membrane permeability of the rat small intestine and Caco-2 cells were examined. LH enhanced the membrane permeability of the rat small intestine, which contains the UWL, via a transcellular route, for which the UWL is the rate limiting factor. The membrane permeability of Caco-2 cells, in which the UWL is insufficient, was not affected by LH. The apparent permeability coefficient (Papp) of a paracellular marker was not significantly altered in the rat small intestine or Caco-2 cells treated with LH at any concentration. Furthermore, the Papp of β-naphthol which is a transcellular marker was not significantly altered in Caco-2 cells treated with LH, but was significantly increased in the rat small intestine in a LH concentration-dependent manner. The present results demonstrate that the physical barrier has an important function in gastrointestinal membrane permeability, and LH-induced changes increase the transcellular permeability of β-naphthol in rat small intestine.

Review on absorption enhancer and bioenhancer

Poor permeability of orally administered drugs is the major factor limiting the bioavailability of orally administered drugs. The unique barrier properties of the gastro-intestinal membrane, intestinal and presystemic metabolism, intersubject variability also contributors to poor permeability and bioavailability of the drugs. Bioenhancer can benefit the drugs with this problem, especially BCS class III and class IV drugs. Different mechanisms have been established to understand the permeation enhancement effect of different permeation enhancers; their understanding can facilitate the selection of suitable absorption promoters for drugs having specific physicochemical properties. However, certain issues associated with development of absorption promoter technology like lack of in vitro and in vivo correlation of efficacy, reproducibility, and safety. Therefore instead of chemical permeation enhancer herbal bioenhancer is more acceptable due to their better safety profile.

Effects of Non-Opioid Analgesics on the Cell Membrane of Skin and Gastrointestinal Cancers.

Skin and gastrointestinal cancer cells are the target of research by many scientists due to the increasing morbidity and mortality rates around the world. New indications for drugs used in various conditions are being discovered. Non-opioid analgesics are worth noting as very popular, widely available, relatively cheap medications. They also have the ability to modulate the membrane components of tumor cells. The aim of this review is to analyze the impact of diclofenac, ibuprofen, naproxen, acetylsalicylic acid and paracetamol on skin and gastrointestinal cancers cell membrane. These drugs may affect the membrane through topical application, at the in vitro and in vivo level after oral or parenteral administration. They can lead to up- or downregulated expression of receptors, transporters and other molecules associated with plasma membrane. Medications may also alter the lipid bilayer composition of membrane, resulting in changes in its integrity and fluidity. Described modulations can cause the visualization of cancer cells, enhanced response of the immune system and the initiation of cell death. The outcome of this is inhibition of progression or reduction of tumor mass and supports chemotherapy. In conclusion, non-opioid analgesics may be used in the future as adjunctive therapy for the treatment of these cancers.

Macroscopic assessment of protective effect of cryopreserved placenta extract in ibuprofen-induced gastroenterocolonopathy

Background. Over-the-counter use of nonsteroidal anti-inflammatory drugs leads to their uncontrolled consumption among the population, which in some cases makes it impossible to prevent and timely detect adverse drug effects, and their effectiveness does not always satisfy clinicians. The purpose was to characterize the cytoprotective properties of cryopreserved placenta extract according to the condition of the mucous membrane of the proximal (esophagus and stomach) and distal (small and large intestine) parts of the gastrointestinal tract on the model of ibuprofen-induced esophagogastroenterocolonopathy. Materials and methods. In vivo experimental studies were performed on 28 male rats. Subchronic ibuprofen-induced gastrointestinal lesions were reproduced by intragastric administration of ibuprofen to rats at a dose of 310 mg/kg. The condition of the gastrointestinal tract mucous membrane was assessed macroscopically on a scale. Results. The therapeutic and prophylactic efficacy of esomeprazole statistically significantly (р < 0.05) took place in the proximal parts of the gastrointestinal tract but had little effect on the prevalence of ulcerative lesions in the intestine. At the same time, unlike esomeprazole, which is known to have only gastroprotective activity, cryopreserved placenta extract had a cytoprotective effect both in the stomach and in the distal parts of the gastrointestinal tract — small and large intestine. Thus, the prevalence of ibuprofen-induced both entero- and colonopathy on the background of the study of the extract was almost twice lower than in rats that did not receive correction drugs. Conclusions. It is established that the use of cryopreserved placenta extract in the treatment-and-prophylactic mode has comparable to esomeprazole gastroprotective activity. In addition, it was found that the use of the studied cryoextract was accompanied by a decrease in the multiplicity of ulcerative defects in the small and large intestine of rats, by 4.6 and 3.8 times, respectively, compared to the control animals.

Recent advances in nanocarriers for nutrient delivery.

For the past few years, there has been a surge in the use of nutraceuticals. The global nutraceuticals market in 2020 was USD 417.66 billion, and the market value is expected to increase by 8.9% compound annual growth rate from 2020 to 2028. This is because nutraceuticals are used to treat and prevent various diseases such as cancer, skin disorders, gastrointestinal, ophthalmic, diabetes, obesity, and central nervous system-related diseases. Nutritious food provides the required amount of nutrition to the human body through diet, whereas most of the bioactive agents present in the nutrients are highly lipophilic, with low aqueous solubility leading to poor dissolution and oral bioavailability. Also, the nutraceuticals like curcumin, carotenoids, anthocyanins, omega-3 fatty acids, vitamins C, vitamin B12, and quercetin have limitations such as poor solubility, chemical instability, bitter taste, and an unpleasant odor. Additionally, the presence of gastrointestinal (GIT) membrane barriers, varied pH, and reaction with GIT enzymes cause the degradation of some of the nutraceuticals. Nanotechnology-based nutrient delivery systems can be used to improve oral bioavailability by increasing nutraceutical stability in foods and GIT, increasing nutraceutical solubility in intestinal fluids, and decreasing first-pass metabolism in the gut and liver. This article has compiled the properties and applications of various nanocarriers such as polymeric nanoparticles, micelles, liposomes, niosomes, solid lipid nanocarriers, nanostructured lipid carrier, microemulsion, nanoemulsion, dendrimers in organic nanoparticles, and nanocomposites for effective delivery of bioactive molecules.

Application of TPGS as an efflux inhibitor and a plasticizer in baicalein solid dispersion

The oral bioavailability and efficacy of baicalein is dramatically limited by its low solubility and effect of efflux. In our study, we chose PVP-VA64 as a carrier and TPGS as a plasticizer and efflux inhibitor to prepare a solid dispersion of baicalein using hot-melt extrusion technology to improve its solubility and bioavailability. The hot-melt process and formulation were optimized, and a BAC-PVP VA64-TPGS solid dispersion (BPT-SD) was prepared. BAC exists in an amorphous or molecular state in BPT-SD. BPT-SD comprised irregular lumps and small particles without BAC or carrier characteristics. The dissolution efficiency of BPT-SD improved under sink conditions. FTIR showed a strong hydrogen bond between BAC and PVP-VA64 in BPT-SD. BPT-SD maintained good physical stability for 6 months. The apparent permeability coefficient of BAC in the Caco-2 cell model confirmed that BPT-SD had higher gastrointestinal membrane permeability. A rat pharmacokinetic study showed that BPT-SD had higher Cmax and AUC0-24h, shorter Tmax, and 2.88-fold higher bioavailability than BAC. A behavioral experiment in chronic unpredictable mild stress (CUMS) mice confirmed the antidepressant efficacy of BAC. BPT-SD reversed depression-like behavior in CUMS mice and improved BAC bioavailability. BAC preparation into a solid dispersion significantly enhanced dissolution performance and bioavailability.

Pseudoboehmite as a drug delivery system for acyclovir

Herpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and it is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of the low permeability across the gastrointestinal membrane. The use of nanoparticles of pseudoboehmite as a drug delivery system in vitro assays is a promising approach to further the permeability of acyclovir release. Here we report the synthesis of high purity pseudoboehmite from aluminium nitrate and ammonium hydroxide containing nanoparticles, using the sol–gel method, as a drug delivery system to improve the systemic bioavailability of acyclovir. The presence of pseudoboehmite nanoparticles were verified by infrared spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. In vivo tests were performed with Wistar rats to compare the release of acyclovir, with and without the addition of pseudoboehmite. The administration of acyclovir with the addition of pseudoboehmite increased the drug content by 4.6 times in the plasma of Wistar rats after 4 h administration. We determined that the toxicity of pseudoboehmite is low up to 10 mg/mL, in gel and the dried pseudoboehmite nanoparticles.

Development of a BCS Class II Drug Microemulsion for Oral Delivery: Design, Optimization, and Evaluation

Our work is aimed at exploring the composition and the properties of microemulsion (ME), as a drug delivery system, to enhance the permeability across the gastrointestinal (GI) barrier of fenofibrate, a BCS class II drug. It is a prodrug that is converted rapidly after oral administration into a major active metabolite which is the fenofibric acid. It undergoes a nearly complete presystemic metabolism. Its main drawback is the low bioavailability of the metabolite. A quick selection of excipients was made based on the capacity of solubilization and the value of hydrophilic-lipophilic balance. The classical method of ME development was coupled with the factorial design in order to minimize the droplet size using a low concentration of surfactant. The optimized ME showed a droplet size of 48.5 nm and physical stability. The passive permeability evaluated using Sartorius was 1.6 times higher than that of the free drug. The ex vivo technique, performed using the everted gut sac model, showed a 2.5-fold higher permeability. This suggests that the carrier-mediated uptake/efflux may present the dominant transport mechanism of fenofibrate. The use of the excipients that inhibit GI P-glycoprotein may be a new perspective. Thus, this paper shows that the composition and the characteristics of ME may be explored to increase the permeability of fenofibrate across the GI membrane.

Rapid Increase of Gastrointestinal P-Glycoprotein Functional Activity in Response to Etoposide Stimulation.

We previously reported that exposure of human colon adenocarcinoma (Caco-2) cells to the bitter substance phenylthiocarbamide (PTC) rapidly enhanced the transport function of P-glycoprotein (P-gp). In this study, we investigated the short-term effect of etoposide, another bitter-tasting P-gp substrate, on P-gp transport function in the same cell line. We found that etoposide exposure significantly increased both the P-gp protein level in the plasma membrane fraction and the efflux rate of rhodamine123 (Rho123) in Caco-2 cells within 10 min. The efflux ratio (ratio of the apparent permeability coefficient in the basal-to-apical direction to that in the apical-to-basal direction) of Rho123 in etoposide-treated cells was also significantly increased compared with the control. These results indicated that etoposide rapidly enhances P-gp function in Caco-2 cells. In contrast, P-gp expression in whole cells at both the mRNA and protein level was unchanged by etoposide exposure, compared with the levels in non-treated cells. Furthermore, etoposide increased the level of phosphorylated ezrin, radixin and moesin (P-ERM) proteins in the plasma membrane fraction of Caco-2 cells within 10 min. P-gp functional changes were blocked by YM022, an inhibitor of cholecystokinin (CCK) receptor. These results suggest that etoposide induces release of CCK, causing activation of the CCK receptor followed by phosphorylation of ERM proteins, which recruit intracellular P-gp for trafficking to the gastrointestinal membrane, thereby increasing the functional activity of P-gp.

Central Composite Design for the Development and Evaluation of Floating-mucoadhesive Tablets of Gliclazide

Background: Gliclazide assimilation rate from the gastrointestinal (GI) tract is slow and inconstant, which may be either due to poor dissolution or poor permeability of the drug across the GI membrane. Objective: The present investigation deals with the formulation of floating-mucoadhesive tablets of gliclazide for oral administration using the central composite design by direct compression technique, using HPMC K4M and Carbopol 934 as release controlling polymers and sodium bicarbonate as an effervescent agent. Methods: Central composite design was employed to quantify the effect of three factorsconcentration of HPMC K4M (X1), the concentration of Carbopol 934 (X2), and concentration of sodium bicarbonate (X3) on floating lag time, drug release and mucoadhesive time of the formulation. Results: The results revealed that floating lag time decreases with a rise in the concentration of sodium bicarbonate, drug release was highest at low levels of HPMC and Carbopol and mucoadhesive time was highest at a high level of Carbopol. Conclusion: The optimized batch (F-7) shows a mucoadhesive time of 23 minutes 27 seconds, floating lag time of 22 seconds and in vitro cumulative percentage of drug release 86.73 % in 10h. From the investigation, it can be summarized that the gastro-retentive drug delivery can be utilized to enhance bioavailability and gastric residence time of the drugs.

К вопросу о клинико-лабораторных особенностях мультисистемного воспалительного синдрома у детей, ассоциированного с SARS-CoV-2

Objective. To analyze clinical manifestations, laboratory parameters, and findings of instrumental examination in children with SARS-CoV-2-related multisystem inflammatory syndrome (MIS). Patients and methods. This study included 60 children aged 1 to 18 years (mean age 8 years) diagnosed with MIS and treated in Khimki Regional Hospital between 06.2020 and 10.2021. All patients underwent standard examination. Results. The majority of MIS patients (87%) were treated in the intensive care unit (ICU) due to severity of their condition; 71% of them were transferred to ICU directly from the admission department. None of children received antiviral therapy upon first encounter with the virus. The proportion of patients with type A blood (group II) was 1.5 times higher than that in the general population. Nine children (15%) were overweight and 5 children (8.3%) were obese. Almost two-thirds of participants (64%) had 3 and 4 systems of organs simultaneously involved in the pathological process. Most commonly, the disease affected the gastrointestinal tract (88%), skin and mucous membranes (77%), cardiovascular system (77%), and urinary tract (43%). Children with MIS were characterized by moderate neutrophilic leukocytosis with a left shift, lymphopenia, thrombocytopenia, anemia, elevated CRP (up to 66x of the upper limit), elevated ferritin (up to 23x of the upper limit), elevated D-dimer, and prolonged aPTT. Conclusion. SARS-CoV-2-related MIS is one of the most severe manifestations of COVID-19 in children, and requires a differential diagnosis with bacterial infections. Key words: children, SARS-CoV-2 infection, multisystem inflammatory syndrome, risk factors

ROSUVASTATIN CALCIUM PRONIOSOME POWDER: A NOVEL APPROACH TO IMPROVE INTESTINAL ABSORPTION AND BIOAVAILABILITY

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of rosuvastatin calcium by improving solubility, dissolution, and/or intestinal permeability.
 Methods: Proniosomal powder formulations were prepared with rosuvastatin calcium drug varying the Span 40 and cholesterol ratio in the range of 0.8:0.2–0.2:0.8 using maltodextrin as carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug:Span 40 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study, and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies.
 Results: Physicochemical studies help in optimization of formulations. Enhancement in dissolution is due to incorporation of rosuvastatin calcium into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Ex vivo studies show significant permeation enhancement across gastrointestinal membrane compared to control.
 Conclusion: Proniosomes provide a powerful and functional way of distribution of inadequately soluble rosuvastatin calcium drug which is proved from in vivo studies based on the enhanced oral delivery.

FORMULATION AND EVALUATION OF OPTIMISED MALTODEXTRIN BASED PRONIOSOME POWDERS CONTAINING BAZEDOXIFENE ACETATE FOR ORAL DELIVERY

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of bazedoxifene acetate by improving solubility, dissolution and/or intestinal permeability.
 Methods: Proniosomal powder formulations were prepared with bazedoxifene acetate drug varying the span 40 and cholesterol ratio in the range of 0.8:0.2 to 0.2:0.8 using maltodextrin as a carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug: span 40 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies.
 Results: Physico-chemical studies help in the optimization of formulations. Enhancement in dissolution is due to the incorporation of bazedoxifene acetate into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Ex vivo studies show significant permeation enhancement across the gastrointestinal membrane compared to control.
 Conclusion: In conclusion, proniosomes provide a powerful and functional way of the distribution of inadequately soluble bazedoxifene acetate drug, which is proved from in vivo studies based on the enhanced oral delivery.

ENHANCED INTESTINAL ABSORPTION AND BIOAVAILABILITY VIA PRONIOSOMES FOR BAZEDOXIFENE ACETATE DRUG

Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of bazedoxifene acetate by improving solubility, dissolution and intestinal permeability.
 Methods: Proniosomal powder formulations were prepared with bazedoxifene acetate drug varying the span 60 and cholesterol ratio in the range of 0.8:0.2 to 0.2:0.8 using maltodextrin as carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug: span 60 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies.
 Results: Physico-chemical studies among various formulations helped in optimization of batch. Good flow properties confirmed from angle of repose values indicate easy filling into capsules. Enhancement in dissolution is due to incorporation of bazedoxifene acetate into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Solid state characterization studies prove the transformation to amorphous form with small particle size improving permeation. No drug excipient interaction was observed and sample is stable in refrigerated conditions. Ex vivo studies show significant permeation enhancement across gastrointestinal membrane compared to control. Invivo studies proved enhanced absorption of bazedoxifene acetate drug by oral route.
 Conclusion: In conclusion, proniosomes provide a powerful and functional way of distribution of inadequately soluble bazedoxifene acetate drug which is proved from in vivo studies based on the enhanced oral delivery.