Natural gum as mucoadhesive controlled release carriers: evaluation of cefpodoxime proxetil by D-optimal design technique.

The present study deals with the development of mucoadhesive controlled release tablets of Cefpodoxime Proxetil to increase the gastric residence time and thus prolong drug release, reduce dosing frequency and improve oral bioavailability. Tablets were prepared using sodium alginate and karaya gum, a natural polymer, with a synthetic polymer hydroxypropylmethylcellulose (K100LV) and Karaya gum with HPMC K100LV in various ratios to optimize the drug release profile using D-Optimal technique. Pre- and post-compression parameters of tablets prepared with various formulations (S1-S9, C1-C9) were evaluated. The FTIR and DSC studies revealed that no physiochemical interaction between excipients and drug. The formulation S7 showed prolonged drug release, and the mechanism of drug release from the optimized formulation was confirmed using the Korsmeyer-Peppas model to be non-Fickian release transport and n value was found 0.605 indicating both diffusion and erosion mechanism from these natural gums. The optimized formulation showed mucoadhesive strength >35 g. An in vivo study was performed on rabbits using an X-ray imaging technique. The radiological evidence suggests that the tablets adheres (more than 10 hours) to a rabbit's stomach. No significant changes were found in the physical appearance, drug content, mucoadhesive study and in vitro dissolution pattern after storage at 40 °C/75% relative humidity for 3 months.

Formulation development and in-vitro/in-vivo correlation for a novel Sterculia gum-based oral colon-targeted drug delivery system of azathioprine.

The present study was aimed at designing a microflora triggered colon-targeted drug delivery system (MCDDS) based on swellable polysaccharide, Sterculia gum in combination with biodegradable polymers with a view to target azathioprine (AZA) in the colon for the treatment of IBD with reduced systemic toxicity. The microflora degradation study of gum was investigated in rat cecal medium. The polysaccharide tablet was coated to different film thicknesses with blends of chitosan/Eudragit RLPO and over coated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid (SGF) (pH 1.2), simulated intestinal fluid (SIF) (pH 6.8) and simulated colonic fluid (SCF) (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudragit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that, the optimized MCDDS was fitted well into first order model and apparent lag time was found to be 6 h, followed by Higuchi spherical matrix release. The degradation of chitosan was the rate-limiting factor for drug release in the colon. In-vivo study in rabbit shows delayed T(max), prolonged absorption time, decreased C(max) and absorption rate constant (Ka) indicating reduced systemic toxicity of the drug as compared to other dosage forms.

In vivo evaluation of modified gum karaya as a carrier for improving the oral bioavailability of a poorly water-soluble drug, nimodipine.

This work examines the influence of modified gum karaya (MGK) on the oral bioavailability of a poorly water-soluble drug, nimodipine (NM), in comparison with that of gum karaya (GK). A cogrinding method was selected to prepare mixtures of NM and GK or MGK in a 1:9 ratio (NM:GK/MGK). Differential scanning calorimetry (DSC), Fourier transmission infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), solubility studies, and in vitro release studies were performed to characterize the properties of the cogrinding mixtures. No drug-carrier interactions were found, as confirmed by DSC and FT-IR studies. The XRD study revealed that the crystallinity of NM was identical in both the cogrinding mixtures and was decreased when compared to that of physical mixtures or pure NM. The in vitro release rate of NM from both cogrinding mixtures was significantly higher than that of physical mixtures or pure NM. The in vivo study revealed that the bioavailability of NM from pure drug was significantly lower when compared to the cogrinding mixtures. The oral bioavailability was found to be NM powder < cogrinding mixtures of NM and GK < cogrinding mixtures of NM and MGK < NM solution. It can be inferred from the above results that MGK, an economical carrier, could be used for the dissolution enhancement of NM.

Nitrogen conversion factors for the proteinaceous content of gums permitted as food additives.

Nitrogen conversion factors for gum arabic (Acacia senegal (L.) Willd.), gum tragacanth (Asiatic Astragalus spp.), gum karaya (Sterculia spp.), guar gum (Cyamopsis spp.), locust bean (carob) gum (Ceratonia spp.), tara gum (Caesalpinia spp.), and xanthan gum (Xanthomonas campestris) have been calculated from data for the amino acid compositions of their proteinaceous components. The factors derived differ from the arbitrary values (5.7 or 6.25) at present specified by international regulatory authorities for some emulsifiers, stabilizers and thickeners.

The absence of rhamnose in human urine following the ingestion of gum karaya (Sterculia).

Urinary rhamnose estimations following ingestion of gum karaya were requested by the Scientific Committee for Food (EEC) in July 1983. Five male volunteers have therefore made 24-h urine collections prior to, and following, the ingestion of 10 g gum karaya for 15 days, an intake ten-fold greater than that approved in terms of the present temporary ADI (0-12 X 5 mg/kg b.w.). Paper chromatographic separations, with two solvent systems, were made on the fresh urine specimens and also after ten-fold enrichments of all urinary constituents. Standard aqueous solutions of rhamnose, and urine to which rhamnose had been added, showed the detection limit to be 0.2 microgram rhamnose. Independent examinations in two laboratories failed to detect rhamnose at this level in any of the urine specimens, Had 1% of the rhamnose present in 10 g gum karaya appeared in the 24-h urine specimens, it would have been detected. This confirms previous evidence that dietary gum karaya is neither digested nor degraded by enteric bacteria and is not absorbed to any significant extent in Man.

A study of the fate of gum karaya in the rat.

Rats were fed a diet containing 5% gum karaya for 24 h and faeces and urine were collected over 72 h. Faeces were examined, after methanolysis, by gas chromatography--mass spectometry and the quantity and monosaccharide composition of the faecal polysaccharide were compared with the dose and original composition of the gum polysaccharide. Gum-derived rhamnose was not found in the urine. Indications of minor quantitative changes in composition but no evidence of extensive degradation or absorption of gum polysaccharide, were found.