Ternary Blends of some Hydrophilic and Hydrophobic Polymers in Colon Targeted Delivery of Metronidazole

Matrix tablets were prepared using blends of xanthan gum (XG), Guar gum (GG) and ethylcellulose (EC). The polymers were combined using six different ratios; 1:1:1, 1:2:1, 1:2:2, 2:2:1, 2:1:2 and 2:1:1 to produce formulations XG1GG1EC1, XG1GG2EC1, XG1GG2EC2, XG2GG2EC1. XG2GG1EC2 and XG2GG1EC1 respectively. Metronidazole was used as the model drug. The ability of the prepared matrices to target drug release predominantly at the colon under the influence of colonic bacteria was evaluated using the dissolution medium containing 4 % caecal content. Our results show that, optimum drug release was observed with formulations XG2GG2EC1 and XG2GG1EC1 with Cmax of 60 and 76 % respectively. Significant difference (P<0.05) was observed between drug release in dissolution medium with and without rat caecal contents for the batches of Metronidazole tablets. Formulations (XG2GG2EC1 and XG2GG1EC1) followed Higuchi square roots kinetics ( r2 =0.9942) via fickian diffusion ( n < 0.45 ) and Korsemeyer model (r2 = 0.9939) via non – fickian diffusion (n > 0.45) respectively. Key Words; matrix.guar, xanthan, ethylcellulose, metronidazole, colon deliver

Effect of drying methods on the powder and compaction properties of microcrystalline cellulose derived from Gossypium herbaceum

The effect of drying method, a process variable, on the powder and compaction properties of microcrystalline cellulose (MCC) obtained from the partial acid hydrolysis of bleached alpha (α) cellulose content of matured linters of Gossypium herbaceum (GH) was investigated. A portion of the wet MCC obtained was fluid bed dried at 60 ± 1 ºC, inlet air of 30 m3 min-1 for 3 h (coded MCC-GossF). The second portion was lyophilized at – 45 ± 2 ºC for 6 h (coded MCC-GossL). The physicochemical, scanning electron micrographs, X ray diffraction patterns and micromeritic properties of the derived MCCs were determined using standard methods. The cohesiveness and compactibility of the powders were investigated using Kawakita model while the deformation and compressibility pattern were determined using Heckel model. Avicel® PH 102 (AV-102) was used as comparing standard. Ash values of < 2%, pH (6.54 ± 0.23 to 6.58 ± 0.08), degree of polymerization, DP (231.50) was obtained. MCC-GossF had higher moisture content, swellability, better flow indices, and lesser porosity than MCC-GossL. Kawakita model demonstrated good consolidation and compactibility for both powders. Compacts of MCC-GossL were significantly (p < 0.05) harder than those of MCC-GossF. Heckel analysis demonstrated good compressibility and deformation pattern that was comparable with AV-102. Compacts of MCC-GossL had better mechanical and tablet compression properties than MCC-GossF. Method of drying significantly (p < 0.05) affected the powder and compaction properties of GH MCC

Ternary Blends of some Hydrophilic and Hydrophobic Polymers in Colon Targeted Delivery of Metronidazole

Matrix tablets were prepared using blends of xanthan gum (XG), Guar gum (GG) and ethylcellulose (EC). The polymers were combined using six different ratios; 1:1:1, 1:2:1, 1:2:2, 2:2:1, 2:1:2 and 2:1:1 to produce formulations XG1GG1EC1, XG1GG2EC1, XG1GG2EC2, XG2GG2EC1. XG2GG1EC2 and XG2GG1EC1 respectively. Metronidazole was used as the model drug. The ability of the prepared matrices to target drug release predominantly at the colon under the influence of colonic bacteria was evaluated using the dissolution medium containing 4 % caecal content. Our results show that, optimum drug release was observed with formulations XG2GG2EC1 and XG2GG1EC1 with Cmax of 60 and 76 % respectively. Significant difference (P<0.05) was observed between drug release in dissolution medium with and without rat caecal contents for the batches of Metronidazole tablets. Formulations (XG2GG2EC1 and XG2GG1EC1) followed Higuchi square roots kinetics ( r2 =0.9942) via fickian diffusion ( n < 0.45 ) and Korsemeyer model (r2 = 0.9939) via non – fickian diffusion (n > 0.45) respectively. Key Words; matrix.guar, xanthan, ethylcellulose, metronidazole, colon deliver

Učinak molekulske mase karboksimetilceluloze i nekih polimera na usporeno oslobađanje teofilina iz hidrofilnih matriksa

The objective of this study was to investigate the influence of the molecular size of carboxymethylcellulose (cmc) and some hydrophobic polymer additives on the release properties of theophylline from the tablet matrices. The cmc matrices were prepared by the conventional wet granulation method. The granules were evaluated for angles of repose, bulk density, compressibility index, and porosity, while the tablets were subjected to hardness, friability and compression characteristics. All the tablet formulations showed acceptable pharmacotechnical properties. Low molecular size cmc (cmc-L) had the fastest drug release t50% values of 27 min, for medium size cmc (cmc-M) 55 min and high molecular size cmc (cmc-H) 200 min. Overall, results showed that drug release rate decreases with increase in molecular size of cmc. All the polymer additives ethylcellulose (ETC), cellulose acetate phthalate (CAP) and Eudragit l-100 (EUD) retarded theophylline release from cmc-L and cmc-H, with ethylcellulose having the most pronounced effect on cmc-L. Kinetic studies using Hixson-Crowell and Peppas-Ritger equations showed that different drug release mechanisms were involved in controlling drug dissolution from the tablets. Drug release mechanism was influenced by both the molecular size of cmc and the presence of polymer additives.U radu je ispitivan učinak molekulske mase karboksimetilceluloze (cmc) i nekih hidrofobnih polimera kao aditiva na profil oslobađanja teofilina iz tabletnih matriksa. Matriksi s cmc pripremljeni su uobičajenom metodom vlažne granulacije. Granulama je određivana sipkost, gustoća, poroznost i indeks kompresivnosti, dok je tabletama ispitivana tvrdoća, rastrošljivost i kompresibilnost. Sve priređene tablete imala su prihvatljiva farmakotehnološka svojstva. Najbrže vrijeme oslobađanja t50% od 27 min postignuto je iz pripravka cmc male molekulske mase (cmc-L), 55 min iz pripravka cmc srednje molekulske mase (cmc-M) 55 min i 200 min iz pripravka cmc velike molekulske mase (cmc-H). Rezultati ukazuju da se brzina oslobađanja smanjuje povećanjem molekulske mase cmc. Svi polimerni aditivi, etilceluloza, celuloza acetat ftalat i Eudragit l-100 usporili su oslobađanje teofilina iz cmc-L i cmc-H pripravka, a najveći učinak imala je etilceluloza na cmc-L. Kinetičke studije provedene pomoću Hixson-Crowell-ove i Peppas-Ritger-ove jednadžbe ukazuju da su u oslobađanju teofilina iz tableta uključeni različiti mehanizmi. Na mehanizam oslobađanja utjecali su i molekulska masa cmc i prisutnost polimernih aditiva

Application of Starch and Starch Derivatives in Pharmaceutical Formulation

Starch is a homo-glucose unit connected with glycosidic linkage. It is well known for its biodegradability, renewability, low cost, flexibility, and availability. However, to reach its potential in the pharmaceutical application, modification is necessary to solve the problem of solubility, retrogradation, and loss of viscosity. In this chapter, we discuss the different physical, chemical, enzymatic, and biotechnological modifications and their subsequent pharmaceutical application both as an excipient and directly as drug delivery vehicles. Overall, there were different characteristics conferred in a modification which were exploited in pharmaceutics, drug delivery, and antimicrobial preparation. We, however, believe that collation of the data on modification would go a long way toward standardizing the application of the modified products

Development of Transdermal Patches for the Delivery of Chlorpheniramine in Infants using Hypromellose and Cassava Starch Composite Polymers

Background: Chlorpheniramine is an antihistamine that is used in the treatment of rhinitis and other allergies. Objectives: The objectives of this research was to develop and evaluate transdermal patches for improved delivery of chlorpheniramine in infants using hypromellose and cassava starch composite polymers. Methods: Chlorpheniramine transdermal patches were formulated by solvent casting method using varying amounts of hypromellose (hydroxypropyl methylcellulose), cassava starch and polyethylene glycol 4000. The formulated transdermal patches were characterized by Fourier Transform Infra-red Spectroscopy (FT-IR), folding endurance, elongation breaking test, percentage moisture uptake/loss and ex vivo permeation studies. Results: The spectra showed no chemical interaction between the ingredients. The transdermal patches showed elastic qualities and high folding endurance. Patches with consistently high moisture uptake (around 40%) were observed to contain high concentration of cassava starch while those with higher amounts of HPMC lost more water (around 35%). The ex vivo study showed efficient permeation and flux for the target purpose. Conclusion: Transdermal patches may be used to deliver low dose chlorpheniramine drug through the skin possibly soft and thin infant skin. Keywords: Transdermal; permeation; flux; allergy; chlorpheniramin

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