Polimerne mješavine obložene Eudragitom: Potencijalni sustav za kontroliranu peroralnu isporuku teofilina

Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl®) formulation. Asmanyl® tablets showed faster absorption (tmax 4.0 h) compared to the TPH formulation, showing a tmax value of 8.0 h. The cmax and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl®, revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline.Pripravci za produljeno oslobađanje (SR) omogućavaju produljeno i kontinuirano oslobađanje lijeka u gastrointestinalnom (GI) traktu i poboljšavaju bioraspoloživost lijekova s uskim apsorpcijskim prozorom. U radu se predlaže nova strategija za razvoj formulacija s produljenim oslobađanjem teofilina (TPH), koja se temelji na sustavu za produljeno oslobađanje, kojem je u svrhu produljenja vremena oslobađanja modificiran način oblaganja i bubrenja. Korišteni su različiti polimeri, kao što su Carbopol 71G (CP), natrijeva karboksimetilceluloza (SCMC), etilceluloza (EC) i njihove kombinacije. Pripravljene matriks tablete obložene su 5-postotnom (m/m) disperzijom Eudragita (EUD) kako bi se postiglo produljeno oslobađanje tijekom 24 h. U pripravljenim formulacijama određena je koncentracija lijeka i in vitro oslobađanje. Rezultati pokazuju da se povećanjem udjela polimera smanjuje brzina oslobađanja in vitro. Oblaganje s EUD značajno je produljilo lag fazu tijekom prva 2 sata otapanja u kiselom pH simuliranog želučanog soka (SGF). Naime, oblaganje usporava ulazak vode i tako smanjuje pogonsku silu za oslobađanje lijeka. Zbog povećane topljivosti obložnog sloja i matriksa u lužnatom mediju, oslobađanje u simuliranoj intestinalnoj tekućini (SIF) je brže. Optimizirana formulacija ispitana je in vivo na zečevima. Farmakokinetički parametri novih formulacija uspoređivani su s komercijalnim pripravkom Asmanyl®. Asmanyl® tablete pokazuju bržu apsorpciju (tmax 4,0 h) u odnosu na TPH formulaciju (tmax 8,0 h). cmax i AUC vrijednosti TPH formulacije bile su značajno (p < 0,05) više od onih za Asmanyl®, što ukazuje na relativnu bioraspoloživost od oko 136,93 %. Stoga smatramo da su polimeri obloženi eudragitom potencijalno korisni za oralnu upotrebu teško topljivog lijeka teofilina

Evaluation of the Anticancer Activity of Bioactive Fraction G Extracted from \u3cem\u3ePavetta crassipes\u3c/em\u3e in Malignant Brain Tumor Cell Lines

Objective: Natural products have served as sources of lead compounds that are commonly used in the treatment of human diseases including cancer. Pavetta crassipes has been widely demonstrated to have ethnopharmacological potential in the management of malaria, gastrointestinal conditions, central nervous system behavioral disorders, hypertension, and cancer. The goal of our study was to evaluate the biological and molecular effects of Fraction G, obtained from the plant Pavetta crassipes, on glioblastoma invasive growth and survival. Methodology: The antiproliferative effects of Fraction G, obtained from Pavetta crassipes, was evaluated using the trypan blue exclusion, (3-(4, 5-Dimethylthiazol- 2yl)-2, 5-Diphenyltetrazolium Bromide; MTT), and lactate dehydrogenase (LDH) assays. Flow cytometry and Western blotting analyses were carried out to examine the effects of Fraction G on cell cycle check-points and its effects on epidermal growth factor receptor-mediated signaling of AKT and MAPK pathways. Results: In this paper, we report that the Fraction G obtained from the plant Pavetta crassipes induced a reduction in glioma cell viability and proliferation as well as induced an increase in apoptosis as evidenced by cleaved PARP, increased caspase 3/7 activity, and cell cycle arrest in the G0/G1 check point. Furthermore, we report that Fraction G inhibited the phosphorylation of AKT and MAPK following EGF treatment. Conclusion: Taken together, our results demonstrate that Fraction G has potent inhibitory effects on pathways involved in glioblastoma proliferation and survival

Powder Compaction: Compression Properties of Cellulose Ethers

Effective development of matrix tablets requires a comprehensive understanding of different raw material attributes and their impact on process parameters. Cellulose ethers (CE) are the most commonly used pharmaceutical excipients in the fabrication of hydrophilic matrices. The innate good compression and binding properties of CE enable matrices to be prepared using economical direct compression (DC) techniques. However, DC is sensitive to raw material attributes, thus, impacting the compaction process. This article critically reviews prior knowledge on the mechanism of powder compaction and the compression properties of cellulose ethers, giving timely insight into new developments in this field

Synthesis, Physicochemical Characterization, And Functional Properties Of An Esterified Starch From An Underutilized Source In Nigeria

Acha ( Digitaria exilis Stapf), also known as Findi, Hungry rice, Petit mil and White fonio, is a small seeded cereal, indigenous to West Africa, which is generally classified as millet. It grows in various parts of Nigeria, Sierra Leone, Ghana, Guinea Bissau and Benin Republic. That species is the most important of a diverse group of wild and domesticated Digitaria species that are harvested in the savannas of West Africa. It is one of the primary cereals of southern Sudan and Ethiopia in Africa. It has potential to improve human nutrition, boost food security, foster rural development and support sustainable use of lands. In this study, acha starch was subjected to modification by acetylation. The acetylated acha starch with degree of modification 0.78 had reduced foaming capacity and amylose contents. The starches have similar organoleptic properties ranging from white, gritty, non sticky to bland tastes. Physicochemical indices investigated such as true density, bulk and tapped densities, water absorption capacity, moisture content, total and acid insoluble ash, and pH were reduced by the acetylation of acha starch. The modification resulted in a significant (P < 0.05) increase in the solubility as well as water and oil absorption capacities of the starch. Scanning electron microscopy revealed starch granules that were predominantly polygonal in shape. Acetylation did not alter the granule morphology. X-ray pattern of the native starch was A type, with similar pattern in the acetylated derivative. Fourier transform infrared spectroscopy (FTIR) results revealed a new band at 1728 cm-1. Thermogravimetry revealed 3 phase decomposition of both the native and modified starches. The acetylation as revealed by Differential scanning calorimetry studies improved the gelation capacity of the native starch and revealed two endothermic peaks and one exothermic peak each for both starches. There was considerable reduction in the peak temperature of gelatinization (Tp) of native starch and a significant (P<0.05) decrease in the enthalpy of gelatinization (DH) was noticed after acetylation

Spasmolytic Activity of Methyl Angolensate: A Triterpenoid Isolated from \u3cem\u3eEntandrophragma angolense\u3c/em\u3e

Entandrophragma angolense is a medicinal plant used in folk medicine against several diseases including peptic ulcer. Methyl angolensate was isolated from E. angolense by recrystallization from methanol. The needlelike crystals were characterized and tested on isolated rabbit jejunum, guinea pig ileum and the rat fundus strip. The compound was also evaluated on the gastrointestinal transit in mice. The results showed that the compound exerted significant concentration dependent inhibition of smooth muscle and reduced the propulsive action of the gastrointestinal tract in mice. The relaxation observed did not attenuate acetylcholine and histamine induced contractions, but was found to inhibit contractions induced by serotonin. It is therefore suggested that methyl angolensate may exert its activity on gastrointestinal smooth muscle via serotonergic mechanisms

Smooth Muscle Contraction Induced by \u3cem\u3eIndigofera dendroides\u3c/em\u3e Leaf Extracts May Involve Calcium Mobilization via Potential Sensitive Channels

The contractile effects of the aqueous extract of the leaves of Indigofera dendroides (ID) were studied on the gastrointestinal motility in mice and isolated smooth muscle preparations obtained from rats and guinea pigs. The contractile effects of 10−6 M acetylcholine, 80 mM KCl and 1.6 mg/ml ID were measured on the rat ileal smooth muscle exposed to calcium-free buffer or physiological solution, to determine the calcium pools mobilized by extract for activation of contraction. Acute toxicity test (LD50) was also carried out in mice. The result showed that ID (0.05–3.2 mg/ml) produced a concentration-dependent contraction of the guinea pig and rat ileum. These responses were not blocked by mepyramine (2.49 × 10−9 M), verapamil (8.14 × 10−9 M), or pirenzepine (4.7 × 10−7 M), but were blocked completely by atropine (2.92 × 10−9 M). A signi.cant increase in propulsion of gastrointestinal motility was observed. Acetylcholine, KCl and ID produced contractions in Ca2+ free media. The phasic components of the contractile responses to Ach as well as the tonic component of K+ and ID-induced contractions were relatively resistant to short periods of calcium-free exposure. Ach, K+ and ID still caused contractions in the presence of verapamil. The data revealed that ID-induced contractions were not mediated by histaminergic receptors, calcium channels, M1 muscarinic receptors. It also suggests that Ach mobilize Ca from some tightly bound or intracellular pool, whereas high K+ and ID may mobilize Ca from some superficial or loosely-bound pool