Particle Engineering of Chitosan and Kaolin Composite as a Novel Tablet Excipient by Nanoparticles Formation and Co-Processing

Chitosan is not a common excipient for direct compression due to poor flowability and inadequate compressibility. Co-processing of chitosan and kaolin is a challenging method to overcome the limitations of the individual excipients. The purpose of the present study was to develop co-processed chitosan–kaolin by the spray drying technique (rotary atomizer spray dryer) and to characterize the excipient properties. The formation of chitosan nanoparticles was the major factor for desirable tablet hardness. The ratio of chitosan/tripolyphosphate of 10:1 and 20:1 had a significant effect on hardness. The successful development of co-processed chitosan–kaolin as a novel tablet excipient was obtained from a feed formulation composed of chitosan and kaolin at a ratio of 55:45 and the optimum chitosan/tripolyphosphate ratio of 20:1. Co-processing altered the physical properties of co-processed chitosan–kaolin in such a way that it enhanced the flowability and tableting performance compared to the physical mixture

Particle Engineering of Chitosan and Kaolin Composite as a Novel Tablet Excipient by Nanoparticles Formation and Co-Processing

Chitosan is not a common excipient for direct compression due to poor flowability and inadequate compressibility. Co-processing of chitosan and kaolin is a challenging method to overcome the limitations of the individual excipients. The purpose of the present study was to develop co-processed chitosan–kaolin by the spray drying technique (rotary atomizer spray dryer) and to characterize the excipient properties. The formation of chitosan nanoparticles was the major factor for desirable tablet hardness. The ratio of chitosan/tripolyphosphate of 10:1 and 20:1 had a significant effect on hardness. The successful development of co-processed chitosan–kaolin as a novel tablet excipient was obtained from a feed formulation composed of chitosan and kaolin at a ratio of 55:45 and the optimum chitosan/tripolyphosphate ratio of 20:1. Co-processing altered the physical properties of co-processed chitosan–kaolin in such a way that it enhanced the flowability and tableting performance compared to the physical mixture

Utilization and Evaluation of Rice Bran and Rice Bran Wax as a Tablet Lubricant

The rice bran and rice bran wax of the KJ CMU107 rice strain were investigated as potential tablet lubricants in a directly compressed tablet formulation. Stabilized full-fatted rice bran (sFFRB), stabilized defatted rice bran (sDFRB), and rice bran wax (RBW) extracted and purified from crude rice bran oil (cRBO) were tested. Two commercial lubricants, including magnesium stearate (MGS) and hydrogenated cottonseed oil (HVO), were employed as the standards in the formulated mixtures, which contained spray-dried rice starch (SDRS) as a diluent. The tableting was carried out for each formulation, and the obtained tablets were physically and mechanically evaluated. Among the parameters investigated were the general appearance, ejection force, weight variation, hardness, friability, and disintegration time. The powder flow was also determined for each formulation. The results showed that the tablet ejection forces for all the lubricated formulations (58–259 N) were significantly lower than that of the non-lubricated control formulation (349 N). The use of sFFRB as a lubricant at 0.5–2.0% w/w could lower the ejection force up to 78%, but the hardness reduced so drastically that the formulations failed the friability test due to the chipping of the tablets’ edges. Moreover, sDFRB performed significantly better as the use at 0.5–1.0% w/w in the formulation helped to lower the ejection forces by up to 80% while maintaining the changes in the tablet hardness within 10%. RBW functioned effectively as a tablet lubricant at a concentration of 0.5% w/w, yielding tablets with good strength comparable to standard HVO lubricant while helping to reduce the ejection force by 82%. In formulations with good lubrication, i.e., friability w/w, with slightly negative effects on the tablet hardness. RBW from KJ CMU107 rice was an effective tablet lubricant at 0.5% w/w, with no effect on tablet hardness. Both materials can be further developed for use as commercial lubricants in direct compression

Fabrication and Characterization of Orodispersible Composite Film from Hydroxypropylmethyl Cellulose-Crosslinked Carboxymethyl Rice Starch

Crosslinked carboxymethyl rice starch (CLCMRS), prepared via dual modifications of native rice starch (NRS) with chloroacetic acid and sodium trimetaphosphate, was employed to facilitate the disintegration of hydroxypropylmethylcellulose (HPMC) orodispersible films (ODFs), with or without the addition of glycerol. Fabricated by using the solvent casting method, the composite films, with the HPMC--LCMRS ratios of 9:1, 7:1, 5:1 and 4:1, were then subjected to physicochemical and mechanical evaluations, including weight, thickness, moisture content and moisture absorption, swelling index, transparency, folding endurance, scanning electron microscopy, Fourier transform infrared spectroscopy, tensile strength, elongation at break, and Young’s modulus, as well as the determination of disintegration time by using the Petri dish method (PDM) and slide frame and bead method (SFM). The results showed that HPMC-CLCMRS composite films exhibited good film integrity, uniformity, and transparency with up to 20% CLCMRS incorporation (4:1 ratio). Non-plasticized composite films showed no significant changes in the average weight, thickness, density, folding endurance (96–122), tensile strength (2.01–2.13 MPa) and Young’s modulus (10.28–11.59 MPa) compared to HPMC film (135, 2.24 MPa, 10.67 MPa, respectively). On the other hand, the moisture content and moisture absorption were slightly higher, whereas the elongation at break (EAB; 4.31–5.09%) and the transparency (4.73–6.18) were slightly lowered from that of the HPMC film (6.03% and 7.03%, respectively). With the addition of glycerol as a plasticizer, the average weight and film thickness increased, and the density decreased. The folding endurance was improved (to >300), while the transparency remained in the acceptable range. Although the tensile strength of most composite films decreased (0.66–1.75 MPa), they all exhibited improved flexibility (EAB 7.27–11.07%) while retaining structural integrity. The disintegration times of most composite films (PDM 109–331, SFM 70–214 s) were lower than those of HPMC film (PDM 345, SFM 229 s). In conclusion, the incorporation of CLCMRS significantly improved the disintegration time of the composite films whereas it did not affect or only slightly affected the physicochemical and mechanical characteristics of the films. The 5:1 and 4:1 HPMC:CLCMRS composite films, in particular, showed promising potential application as a film base for the manufacturing of orodispersible film dosage forms

Formulation Study of a Co-Processed, Rice Starch-Based, All-in-One Excipient for Direct Compression Using the SeDeM-ODT Expert System

A co-processed, rice starch-based excipient (CS), previously developed and shown to exhibit good pharmaceutical properties, is investigated as an all-in-one excipient for direct compression (DC). An SeDeM-ODT expert system is applied to evaluate the formulation containing CS, in comparison with those containing the physical mixture and the commercial DC excipients. The results revealed that CS showed acceptable values in all six incidence factors of the SeDeM-ODT diagram. In addition, the comprehensive indices (IGC and IGCB) were higher than 5.0, which indicated that CS could be compressed with DC technique without additional blending with a disintegrant in tablet formulation. The formulation study suggested that CS can be diluted up to 60% in the formulation to compensate for unsatisfactory properties of paracetamol. At this percentage, CS-containing tablets exhibited narrow weight variation (1.5%), low friability (0.43%), acceptable drug content (98%), and rapid disintegration (10 s). The dissolution profile of CS displayed that more than 80% of the drug content was released within 2 min. The functionality of CS was comparable to that of high functionality excipient composite (HFEC), whereas other excipients were unsuccessful in formulating the tablets. These results indicated that CS was a suitable all-in-one excipient for application in DC of tablets

Biodegradable and Nontoxic Nanogels as Nonviral Gene Delivery Systems

The development of polymeric systems with tailored properties as nonviral gene carriers continues to be a challenging and exciting field of research. We report here the synthesis and characterization of biodegradable, temperature- and pH-sensitive carbohydrate-based cationic nanogels as effective gene delivery carriers to Hep G2 cells. The temperature-sensitive property of the nanogels allows their facile complexation of DNA, while the pH-sensitive property allows the degradation of nanogels followed by the release of plasmid in the endosome. The nanogels are synthesized via reversible addition–fragmentation chain transfer polymerization (RAFT) technique and are evaluated for their DNA condensation efficacy. The gene delivery efficacies of these nanogels are subsequently studied and it is found that these cationic glyconanogels can serve as potent gene delivery vectors in hepatocytes. It is found that the gene delivery efficacies of this system are similar to that of branched poly­(ethyleneimine), which is used as a positive control. Moreover, these nanogels show desirable properties for systemic applications including low toxicity and degradation in acidic environment