Formulation development and in-vitro evaluation of gastroretentive drug delivery system of loxoprofen sodium: A natural excipients based approach.

The limitations of conventional type delivery systems to retain drug (s) in the stomach has resulted in the development of novel gastroretentive drug delivery system. We developed single-layer effervescent floating tablets of loxoprofen sodium for prolong delivery in the stomach using natural polymers xanthan gum, guar gum and semisynthetic polymer HPMCK4M. All the formulations (F1-F9) were developed by varying concentrations of xanthan gum and HPMCK4M while guar gum concentration was kept constant. Two gas generating agent (s) incorporated were sodium bicarbonate and citric acid. All compendial pre and post-compression tests results were in the acceptable limits. FTIR analysis confirmed drug-polymer compatibility. The in-vitro drug release in simulated conditions i.e., 0.1 N HCl for 12 h revealed orderly increase in total floating time, i.e., less than 6 h for F1 over 12 h for F9. Formulations F1 to F4 were not capable to retard drug release up to 12 h, whereas F5-F7 for 12 h, while F8 and F9 for more than 12 h. Data fitting in various kinetic models showed that drug release best fit in first order kinetic model and F9 in zero order. Based on results data, F7 was the best among all.

Acrylamide grafted neem (Azadirachta indica) gum polymer: Screening and exploration as a drug release retardant for tablet formulation.

The study was initiated with the intent to synthesize acrylamide grafted neem gum polymer (AAm-g-NG), and screen its drug release retardation ability both in vitro and in vivo. Different batches (NGP-1 to NGP-9) of tablet formulation were prepared by varying polymer concentration using propranolol HCl and compared with HPMC K100 M and marketed SR tablets. FTIR study proved the grafting phenomenon and showed no incompatibility between AAm-g-NG and propranolol HCl. AAm-g-NG showed significant swelling and water retention capacity than NG. AAm-g-NG was found to be biodegradable and exhibited no toxicity to Artemia salina. After 12 h, NGP-6 showed non-significant (p > 0.05; f2= ∼ 90) percent drug release (80.52 ±â€¯3.41%) compare to marketed formulation (79.65 ±â€¯4.08%). Significant swelling of the matrix caused slower diffusion of the drug. NGP-6 and marketed formulation in rabbits showed the non-significant difference between Cmax and Tmax, hence NGP-6 meets the requirement of sustained-release tablets.

Poly(hydroxybutyrate-co-hydroxyvalerate) microparticles embedded in κ-carrageenan/locust bean gum hydrogel as a dual drug delivery carrier.

A novel composite hydrogel was prepared as a dual drug delivery carrier. Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles were prepared to encapsulate simultaneously ketoprofen and mupirocin, as hydrophobic drug models. These microparticles were embedded in a physically crosslinked hydrogel of κ-carrageenan/locust bean gum. This composite hydrogel showed for both drugs a slower release than the obtained release from microparticles and hydrogel separately. The release of both drugs was observed during a period of 7 days at 37 °C. Different kinetic models were analyzed and the results indicated the best fitting to a Higuchi model suggesting that the release was mostly controlled by diffusion. Also, the drug loaded microparticles were spherical with average mean particle size of 1.0 µm, mesoporous, and distributed homogeneously in the hydrogel. The composite hydrogel showed a thermosensitive swelling behavior reaching 183% of swelling ratio at 37 °C. The composite hydrogel showed the elastic component to be higher than the viscous component, indicating characteristics of a strong hydrogel. The biocompatibility was evaluated with in vitro cytotoxicity assays and the results indicated that this composite hydrogel could be considered as a potential biomaterial for dual drug delivery, mainly for wound healing applications.

Preparation of Chitosan Okra Nanoparticles: Optimization and Evaluation as Mucoadhesive Drug Delivery System.

OBJECTIVE: To prepare chitosan-okra gum nanoparticles and their evaluation as mucoadhesive drug delivery system for intranasal delivery of esculin. METHOD: Esculin loaded chitosan-okra gum based nanoparticles were prepared using ionic gelation method. The preparation method was optimized using Box-Behnken experimental design employing okra gum concentration, chitosan concentration, pH and stirring speed as independent variables and particle size, encapsulation efficiency and zeta potential of the formulation were selected as dependent variables. The optimized formulation was characterized using FTIR, SEM and TEM. The nanoparticles were evaluated for their bioadhesive strength and in vitro drug release studies. The optimized intranasal formulation was administered to rats and the pharmacokinetic profile and biodistribution studies were carried out to calculate the targeting efficiency of the formulation in the brain. RESULTS: The nanoparticles were found to depict particle size in the range of 294.0 to 613.4 nm. The concentration of gums was found to significantly influence the particle size and encapsulation efficiency. The nanoparticles depicted bioadhesive strength of 32±2%. The in vitro drug release studies showed 96.4±4.2% release of esculin from nanoparticles in 4h. The drug targeting of NPs to brain was found to be nearly double that of esculin given as simple solution. CONCLUSION: The nanoparticles prepared using chitosan-okra gum were found to possess good mucoadhesive strength with and high brain targeting efficiency.

In-vitro and In-vivo Pharmacokinetic Evaluation of Guar Gum-Eudragit® S100 Based Colon-targeted Spheroids of Sulfasalazine Co-administered with Probiotics.

BACKGROUND: Polysaccharide based delivery systems have been successfully used to target drugs to colon. In some recent reports, the superiority of concomitant administration of probiotics with such systems has been established. However, the pharmacokinetics of such symbiotic therapy remain unexplored hitherto. METHODS: This study deciphers the pharmacokinetic parameters of guar gum based colon targeted spheroids of sulfasalazine with co-administration of probiotics in experimental rats. Thirty rats were divided into five groups using Latin square design. These were subjected to treatment with delayed release formulation, uncoated spheroids, coated spheroid and coated spheroids along with probiotics. RESULTS: In case of delayed release formulation, negligible presence of sulfasalazine in plasma was observed in first 2h, followed by significant increase in sulfasalazine concentration after 3h. Higher plasma concentrations of sulfasalazine were detected for uncoated spheroids with and without probiotics. Negligible release of drug upto 5h and delayed Tmax in case of guar-gum coated sulfasalazine spheroids with or without probiotics clearly indicated successful formulation of colon targeted spheroids. Further, for coated spheroids (both with and without probiotics), the value of Tmax is found to be significantly higher than those with the other treatments. CONCLUSION: Colon targeted spheroids were therefore, found to reduce absorption of drug which, in turn, is expected to reduce the side effects as only local action in colon is required for treatment of colitis. This is the first report on pharmacokinetic study of a colon targeted delivery system co-administered with probiotics.

Araucaria Gum: Novel Natural Polymer for Controlled Drug Delivery. Development, In Vitro and In Vivo Evaluation of Araucaria Gum Based Matrix Tablets for Controlled Release.

CONTEXT: Assessment of natural polymers in oral controlled drug delivery. OBJECTIVE: The objective of the present investigation was to assess of Araucaria gum (AHG) obtained from bark exudates of the Araucaria heterophylla (family: Araucariaceae) for the design of oral controlled release forms, in particular tablet dosage forms by using matrix systems. Diclofenac sodium was used as model drug and compared with the marketed formulation. METHOD: Matrix tablets were prepared by wet granulation technique and 5% w/v of AHG dispersion water was used as granulating agent for preparation of AHG matrix tablets. RESULTS: AHD2 (3:20) was found to be the optimized formulation based on in vitro drug dissolution studies. FTIR and DSC studies performed on the optimized formulations indicated no drug-polymer interaction. AHD2 (3:20) was found to be stable after accelerated stability testing for 6 months as per ICH guidelines. Pharmacokinetic studies of the optimized formulation were performed in healthy Albino Wister rabbits in comparison with that of the pure drug by estimating pharmacokinetic parameters and mean residence time (MRT). It was found that there is a significant increase in the bioavailability of diclofenac sodium from AHD2 formulation which was evident from the high AUC and MRT values compared with the pure drug. CONCLUSION: The above results clearly indicated that AHG gum can be used for the development of oral controlled release dosage forms by using matrix systems.

Starch-free grewia gum matrices: Compaction, swelling, erosion and drug release behaviour.

Polysaccharides are suitable for application as hydrophilic matrices because of their ability to hydrate and swell upon contact with fluids, forming a gel layer which controls drug release. When extracted from plants, polysaccharides often contain significant quantities of starch that impacts upon their functional properties. This study aimed to evaluate differences in swelling, erosion and drug release from matrix tablets prepared from grewia gum (GG) and starch-free grewia gum (GDS) extracted from the stems of Grewia mollis. HPMC was used as a control polymer with theophylline as a model drug. Swelling, erosion, and in-vitro release were performed in deionized water, pH 1.2 and pH 6.8 media. The Vergnaud and Krosmeyer-Peppas model were used for swelling and drug release kinetics, respectively. However, linear regression technique was used to determine the erosion rate. GDS compacts were significantly harder than the native GG and HPMC compacts. GDS matrices exhibited the fastest erosion and drug release in deionised water and phosphate buffer compared with the GG and HPMC. At pH 1.2, GDS exhibited greater swelling than erosion, and drug release was similar to GG and HPMC. This highlights the potential of GDS as a matrix for controlled release similar to HPMC and GG at pH 1.2 but with a more rapid release at pH 6.8. GDS may have wider application in reinforcing compacts with relatively low mechanical strength.

Locust bean gum safety in neonates and young infants: an integrated review of the toxicological database and clinical evidence.

Locust bean gum (LBG) is a galactomannan polysaccharide used as thickener in infant formulas with the therapeutic aim to treat uncomplicated gastroesophageal reflux (GER). Since its use in young infants below 12weeks of age is not explicitly covered by the current scientific concept of the derivation of health based guidance values, the present integrated safety review aimed to compile all the relevant preclinical toxicological studies and to combine them with substantial evidence gathered from the clinical paediatric use as part of the weight of evidence supporting the safety in young infants below 12weeks of age. LBG was demonstrated to have very low toxicity in preclinical studies mainly resulting from its indigestible nature leading to negligible systemic bioavailability and only possibly influencing tolerance. A standard therapeutic level of 0.5g/100mL in thickened infant formula is shown to confer a sufficiently protective Margin of Safety. LBG was not associated with any adverse toxic or nutritional effects in healthy term infants, while there are limited case-reports of possible adverse effects in preterms receiving the thickener inappropriately. Altogether, it can be concluded that LBG is safe for its intended therapeutic use in term-born infants to treat uncomplicated regurgitation from birth onwards.

Evaluation of Prunus domestica gum as a novel tablet binder

To evaluate binding potential of Prunus domestica gum in tablets formulations. Six tablet batches (F-1B to F-6B) were prepared by wet granulation method, containing Avicel pH 101 as diluent, sodium diclofenac as model drug using 10, 15 and 20 mg of Prunus domestica gum as binder and PVP K30 was used as standard binder. Magnesium stearate was used as lubricant. Flow properties of granules like bulk density, tapped density, Carr index, Hausner’s ratio, angle of repose as well as physical parameters of the compressed tablets including hardness, friability, thickness and disintegration time were determined and found to be satisfactory. The FTIR spectroscopic analysis showed that the formulation containing plant gum is compatible with the drug and other excipients used in tablets formulation. Hence the plant gum has role as a potential binder in tablets formulations. The dissolution profile showed that tablets formulations containing Prunus domestica gum 15 mg/200 mg of total weight of tablet as binder showed better results as compared to PVP K30.

Para avaliar a propriedade aglutinante da goma Prunus domestica em formulações de comprimidos, seis lotes (F-1B para F-6B) foram preparados pelo método de granulação úmida, contendo Avicel pH 101 como diluente e diclofenaco de sódio como fármaco modelo, usando 10, 15 e 20 mg de goma de Prunus domestica como agente aglutinante e PVP K30 como aglutinante padrão. O estearato de magnésio foi utilizado como lubrificante. Propriedades de fluxo dos grânulos, como a densidade, índice de Carr, razão de Hausner, ângulo de repouso, bem como parâmetros físicos dos comprimidos, incluindo o tempo de dureza, friabilidade, espessura e desintegração foram determinados e se mostraram satisfatórios. A análise espectroscópica no FTIR mostrou que a formulação contendo goma vegetal é compatível com o fármaco e outros excipientes utilizados na formulação dos comprimidos. Assim, a goma vegetal tem papel potencial como aglutinante em formulações de comprimidos. O perfil de dissolução das formulações que contêm 15 mg/200 mg do peso total do comprimido em goma de Prunus domestica como aglutinante mostrou melhores resultados comparativamente ao PVP K30.

Antiarthritic and chondroprotective activity of Lakshadi Guggul in novel alginate-enclosed chitosan calcium phosphate nanocarriers.

AIM: This study aimed to evaluate the antiarthritic and chondroprotective potentials of Lakshadi Guggul (LG) and Cissus quadrangularis encapsulated in novel alginate-enclosed chitosan-calcium phosphate nanocarriers (NCs) both in vitro in primary human chondrocytes and in vivo in mice with collagen-induced arthritis. MATERIALS & METHODS: Chondrocytes exposed to IL-1ß and osteoarthritis chondrocytes grown in an ex vivo inflammation-based coculture were incubated with different concentrations of herbals, and cell modulatory activities were determined. For in vivo studies, herbals and their encapsulated nanoformulations were administered orally to DBA/1 mice with collagen-induced arthritis. RESULTS: C. quadrangularis and LG showed enhanced chondroprotective and proliferative activity in IL-1ß-exposed primary chondrocytes, with LG showing the highest therapeutic potency. LG increased viability, proliferative and mitogenic activity, and inhibited cell apoptosis and mitochondrial depolarization. In vivo studies with LG and alginate-enclosed chitosan-calcium phosphate LG NCs revealed cartilage regenerative activity in those administered with the nanoformulation. The NCs were nontoxic to mice, reduced joint swelling and paw volume, and inhibited gene expression of MMPs and cytokines. CONCLUSION: The promising results from this study reveal, for the first time, the novel polymeric NC encapsulating LG as a potential therapeutic for rheumatic diseases.

The effect of processing variables on the mechanical and release properties of tramadol matrix tablets incorporating Cissus populnea gum as controlled release excipient.

BACKGROUND: Natural gums are polymers widely used as excipients in drug formulation. Polymer extraction and formulation processing methods could significantly affect formulation characteristics. OBJECTIVES: To evaluate different methods of gum extraction and the effect of different compression methods on the mechanical and release properties of tramadol hydrochloride matrix tablets incorporating cissus gum as controlled release polymer. MATERIAL AND METHODS: Water (CW) and acetone (CA) extracts of cissus gum were obtained from Cissus populea stem and two methods - wet granulation and direct compression - were used to compress the tablet and compare it with xanthan gum (X) formulations. Crushing strength and friability were used to assess mechanical properties while dissolution rate were used to assess release properties. Data were analysed using t-test and ANOVA at p < 0.05. RESULTS: The crushing strength of tramadol tablets has increased together with the increase in polymer concentration in all formulations, while friability has decreased for both methods. Tablets made by wet granulation had higher crushing strength than those made by direct compression method. The release mechanism for both direct compression and wet granulation methods was Fickian and non-Fickian respectively. The rank order for t25, t50 and t75 for all formulations was X > CA > CW. Generally, wet granulation method decreased the rate of tramadol release more than direct compression method, indicating a higher drug retarding ability. CONCLUSIONS: Incorporation of cissus gum controlled the release of tramadol hydrochloride from the matrix tablets. Extraction method and formulation variables influenced mechanical and release properties of the tablets. Cissus gum acetone extract had comparable release properties with xanthan gum and could serve as a cheaper alternative in controlled release tablet formulations.

Acute liver failure caused by 'fat burners' and dietary supplements: a case report and literature review.

Globally, people are struggling with obesity. Many effective, nonconventional methods of weight reduction, such as herbal and natural dietary supplements, are increasingly being sought. Fat burners are believed to raise metabolism, burn more calories and hasten fat loss. Despite patient perceptions that herbal remedies are free of adverse effects, some supplements are associated with severe hepatotoxicity. The present report describes a young healthy woman who presented with fulminant hepatic failure requiring emergent liver transplantation caused by a dietary supplement and fat burner containing usnic acid, green tea and guggul tree extracts. Thorough investigation, including histopathological examination, revealed no other cause of hepatotoxicity. The present case adds to the increasing number of reports of hepatotoxicity associated with dietary supplements containing usnic acid, and highlights that herbal extracts from green tea or guggul tree may not be free of adverse effects. Until these products are more closely regulated and their advertising better scrutinized, physicians and patients should become more familiar with herbal products that are commonly used as weight loss supplements and recognize those that are potentially harmful.

Preparation and characterization of cross-linked guar gum microspheres: optimization using factorial design.

In the present work cross-linked guar gum microspheres were prepared for colon specific delivery of ornidazole. Development and optimization of guar gum microspheres for colonic drug delivery was carried out using a 2(4) factorial design based on four independent variables. Microspheres were prepared by emulsification method using glutaraldehyde as cross-linking agent. Morphology and surface characteristics of the formulations were determined by scanning electron microscopy. Particle size of the guar gum microspheres was determined by particle size analyzer. In vitro drug-release studies were performed in conditions simulating stomach-to-colon transit in the presence and absence of rat cecal contents. Only a small fraction of drug was released at acidic pH; however, the release of drug was found to be higher in the presence of rat cecal contents, indicating the susceptibility of guar gum matrix to colonic enzymes released from rat cecal contents. The significance of differences was evaluated by analysis of variance (ANOVA). Differences were considered statistically significant at p<0.05.

pH-enzyme di-dependent chronotherapeutic drug delivery system of theophylline for nocturnal asthma.

The purpose of this research work was to develop and evaluate a chronotherapeutic based colon-targeted drug delivery system of theophylline (THEO) exploiting pH-enzyme sensitive property for the prevention of episodic attack of asthma in early morning. Guar gum microspheres of theophylline were prepared by emulsification technique. Coating of microspheres was performed using solvent evaporation method with pH sensitive Eudragit(®) polymers. The particle size and surface morphology, entrapment efficiency and degree of swelling of microspheres were examined. The in vitro drug release studies were performed in pH progression medium and also in the presence of 2% rat caecal content. Theophylline was efficiently microencapsulated in guar gum microspheres at different polymer concentrations (1-4%). Fourier transform infrared (FT-IR)-spectroscopy confirmed the intermolecular interactions between guar gum and glutaraldehyde. Coating of guar gum microspheres by Eudragit led to decelerate the in vitro drug release of THEO. Moreover in vitro drug release studies also performed with 2% rat caecal content showed marked increment in drug release. The controlled release of THEO after a lag time was achieved with developed formulation for chronotherapeutic delivery. The pH dependent solubility behavior of Eudragit and gelling properties of guar gum are found to be responsible for delaying the release.

Oral sustained release tablets of zidovudine using binary blends of natural and synthetic polymers.

Oral sustained release matrix tablets of zidovudine (ZDV) were prepared using different types, proportions and blends of carbopol 71G (C71) and a plant gum obtained from Abelmoschus esculentus (AEG). The effect of various formulation factors like polymer proportion, polymer type and pH of the dissolution medium on the in vitro release of the drug was studied, using the half change technique, in 900 ml of dissolution medium, at 100 rpm. Release kinetics were analyzed using Zero-order, Higuchi's square-root and Ritger-Peppas' empirical equations. In vitro release performance as revealed by the time taken for 70% of the drug to be released (t70%), showed that the release rate decreased with increase in polymer proportion. Matrix tablets containing 10 and 20% AEG were found to exhibit immediate-release characteristics. Matrix tablets containing 30% AEG showed t70% value of 204 min and extended the release up to 5 h, while matrix tablets containing 30% carbopol showed t70% value of 234 min and extended the release up to 6 h. Three blends of AEG and C71 at the ratio of 1:2, 2:1 and 1:3 showed t70% values of 132, 312 and 102 min respectively and extended the release up to 8 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed Fickian and anomalous release. Drug release from matrix tablets of zidovudine containing blends of AEG and C71 demonstrates the advantage of blending a natural and synthetic polymer over single polymer use.

Rheological characterization and drug release studies of gum exudates of Terminalia catappa Linn.

The present study was undertaken to evaluate the gum exudates of Terminalia catappa Linn. (TC gum) as a release retarding excipient in oral controlled drug delivery system. The rheological properties of TC gum were studied and different formulation techniques were used to evaluate the comparative drug release characteristics. The viscosity was found to be dependent on concentration and pH. Temperature up to 60 degrees C did not show significant effect on viscosity. The rheological kinetics evaluated by power law, revealed the shear thinning behavior of the TC gum dispersion in water. Matrix tablets of TC gum were prepared with the model drug dextromethorphan hydrobromide (DH) by direct compression, wet granulation and solid dispersion techniques. The dissolution profiles of the matrix tablets were compared with the pure drug containing capsules using the USP Basket apparatus with 500 ml phosphate buffer of pH 6.8 as a dissolution medium. The drug release from the compressed tablets containing TC gum was comparatively sustained than pure drug containing capsules. Even though all the formulation techniques showed reduction of dissolution rate, aqueous wet granulation showed the maximum sustained release of more than 8 h. The release kinetics estimated by the power law revealed that the drug release mechanism involved in the dextromethorphan matrix is anomalous transport as indicated by the release exponent n values. Thus the study confirmed that the TC gum might be used in the controlled drug delivery system as a release-retarding polymer.