Evaluation of Prosopis africana Seed Gum as an Extended Release Polymer for Tablet Formulation

In the present work, an attempt has been made to screen Prosopis africana seed gum (PG), anionic polymer for extended release tablet formulation. Different categories of drugs (charge basis) like diclofenac sodium (DS), chlorpheniramine maleate (CPM), and ibuprofen (IB) were compacted with PG and compared with different polymers (charge basis) like xanthan gum (XG), hydroxypropyl methyl cellulose (HPMC-K100M), and chitosan (CP). For each drug, 12 batches of tablets were prepared by wet granulation technique, and granules were evaluated for flow properties, compressibility, and compactibility by Heckel and Leuenberger analysis, swelling index, in vitro dissolution studies, etc. It has been observed that granules of all batches showed acceptable flowability. According to Heckel and Leuenberger analysis, granules of PG-containing compacts showed similar and satisfactory compressibility and compactibility compared to granules of other polymers. PG showed significant swelling (P < 0.05) compared to HPMC, and better than CP and XG. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) study showed no interaction between drugs and polymers. From all PG-containing compacts of aforesaid drugs, drug release was sustained for 12 h following anomalous transport. Especially, polyelectrolyte complex formation retarded the release of oppositely charged drug (CPM-PG). However, extended release was noted in both anionic (DS) and nonionic (IB) drugs, maybe due to swollen gel. All compacts were found to be stable for 3-month period during stability study. This concludes that swelling and release retardation of PG has close resemblance to HPMC, so it can be used as extended release polymer for all types of drugs.KEY WORDS: chlorpheniramine maleate, diclofenac sodium, extended release, ibuprofen, Prosopis africana     

Controlled Microwave Processing Applied to the Pharmaceutical Formulation of Ibuprofen

The first successful development of controlled microwave processing for pharmaceutical formulations is presented and illustrated with a model drug (ibuprofen) and two excipients (stearic acid and polyvinylpyrrolidone). The necessary fine temperature control for formulation with microwave energy has been achieved using a uniquely modified microwave oven with direct temperature measurement and pulse-width modulation power control. In addition to comparing microwave and conventional heating, the effect of the presence of liquid (water) in aiding the mixing of the drug and excipient during formulation was also investigated. Analysis of the prepared formulations using differential scanning calorimetry and dissolution studies suggest that microwave and conventional heating produce similar products when applied to mixtures of ibuprofen and stearic acid. However, the differences were observed for the ibuprofen and polyvinylpyrrolidone formulation in terms of the dissolution kinetics. In all cases, the presence of water did not appear to influence the formulation to any appreciable degree. The application of controllable microwave heating is noteworthy as fine temperature control opens up opportunities for thermally sensitive materials for which microwave methods have not been feasible prior to this work.     

Formulation and Evaluation of Bi-layer Tablet of Metoclopramide Hydrochloride and Ibuprofen

The aim of this study was to prepare bi-layer tablet of Metoclopramide Hydrochloride (MTH) and Ibuprofen (IB) for the effective treatment of migraine. MTH and IB were formulated as immediate and sustained release layer respectively. MTH was formulated as immediate release layer by using various disintegrants like Ac-Di-Sol, Polyplasdone XL, Explotab, Agar and Gellan Gum. Treated form of gellan gum and agar was prepared and compared for their disintegrant efficiency with other disintegrants. IB was formulated as sustained release layer using hydrophilic matrix (hydroxypropylmethylcellulose [HPMC K₄M]). The effect of concentration of hydrophilic matrix (HPMC K₄M), binder (polyvinylpyrollidone [PVP K₃₀]) and buffer (sodium bicarbonate) on IB release was studied. The dissolution study of sustained release layer showed that an increasing amount of HPMC or PVP K₃₀ results in reduced IB release. The inclusion of buffer (sodium bicarbonate) enhanced the release of IB from sustained release layer. The rational for formulation of bi-layer tablet of these two drugs in combination was (1) MTH increases the absorption of acidic non-steroidal anti-inflammatory drug (NSAID) by increasing gastric motility. So sequential release of MTH (as immediate release) and IB (as sustained release) was suitable for treatment of migraine. (2) MTH was degraded when prolonged contact with acidic NSAID. Bi-layer tablet was suitable for preventing direct contact of these two drugs and thus to maximize the efficacy of combination of two drugs for migraine.     

Formulation of Eco-friendly Medicated Chewing Gum to Prevent Motion Sickness

An attempt was made to formulate medicated chewing gum to prevent motion sickness using natural gum base for faster onset of action and easy administration, anywhere and anytime, without access to water. To avoid the discard issue of gum cud, natural gum base of Triticum aestivum (wheat grain) was explored because of its biodegradable and biocompatible nature and easy availability. Prolamin, extracted from wheat, showed good chewing capacity, elasticity, high water retention capacity, antifungal activity, and compatibility with the drug. Formulations were prepared based on a two-factor and three-level factorial design. Amount of calcium carbonate (texturizer) and gum base were selected as independent variables. Elasticity and drug release were considered as the dependent variables. All batches were evaluated for the content uniformity, elasticity study, texture study, in vitro drug release study, and chewiness study. Results revealed that medicated chewing gum containing 80 mg of calcium carbonate and 500 mg of gum base showed good elasticity and more than 90% drug release within 16 min. Thus, this study suggested that both good elasticity and chew ability and abundant availability of wheat grain can act as a potential gum base for medicated chewing gum.KEY WORDS: biodegradable gum, gum base, medicated chewing gum, plasticizer, wheat prolamin     

Effect of Gum Arabic,Gum Ghatti and Sugar Beet Pectin as Interfacial Layer on Lipid Digestibility in Oil-in-Water Emulsions

The impact of gum arabic (GA), ghatti gum (GG), and sugar beet pectin (SBP) on the digestion rate of emulsified lipids is investigated in vitro under model duodenal digestion condition. The aim was to understand the role of the interfacial layer surrounding the lipid droplets on lipid hydrolysis in order to control lipid digestion. The emulsifier concentration required to provide the same emulsion droplet size decreased in the order: GA > GG > SBP, demonstrating the best emulsifying activity of SBP. The rate and extent of free fatty acid release during lipid digestion did not differ significantly among the three types of gums in emulsions with D[2,3] < 2 μm. However, considerable difference was observed in emulsions with D[2,3] > 2 μm, and the digestive rate decreased in the order: GA > SBP > GG. The difference in digestion rate was attributed to the stability of the emulsified lipid droplets in the stimulated intestinal juice and the resistance of interfacial layer against displacement by bile salts. The difference of resisting against displacement by bile salts for the interfacial layers was detected with bile salts concentration of 0.025 mg/mL, and all of the pre-adsorbed emulsifiers could be completely displaced from interface by bile salts at 5 mg/mL. Emulsions with SBP were susceptible to Ca²⁺ and Na⁺ in simulated intestinal juice, resulting in the flocculation and coalescence of emulsion droplets. A reduction of the surface area of lipids would contribute to a slow digestion. Emulsion stabilized by GG was very effective at retarding lipolysis mainly due to the affinity of linked protein moieties of GG and its hydrophobic binding with bile salts. The knowledge gained in the study has important implications in designing proper emulsion-based systems for controlling lipid digestibility at specific sites within the gastrointestinal tract.     

Neem Gum as a Binder in a Formulated Paracetamol Tablet with Reference to Acacia Gum BP

This study determined the physical, compressional, and binding properties of neem gum (NMG) obtained from the trunk of Azadirachta indica (A Juss) in a paracetamol tablet formulation in comparison with official Acacia gum BP (ACA). The physical and flow properties were evaluated using density parameters: porosity, Carr’s index, Hausner’s ratio, and flow rate. Compressional properties were analyzed using Heckel and Kawakita equations. The tensile strength, brittle fracture index, and crushing strength–friability/disintegration time ratio were used to evaluate the mechanical properties of paracetamol tablets while the drug release properties of the tablets were assessed using disintegration time and dissolution times. Tablet formulations containing NMG exhibited faster onset and higher amount of plastic deformation during compression than those containing ACA. Neem gum produced paracetamol tablets with lower mechanical strength; however, the tendency of the tablets to cap or laminate was lower when compared to those containing ACA. Inclusion of NMG improved the balance between binding and disintegration properties of paracetamol tablets produced than those containing ACA. Neem gum produced paracetamol tablets with lower disintegration and dissolution times than those containing ACA.     

Design and Evaluation of the Release Characteristics of Caffeine-Loaded Microcapsules in a Medicated Chewing Gum Formulation

The aim of this study was to microencapsulate caffeine by the emulsion technique, trying to control its release from a medicated chewing gum. Three formulations were prepared using alginate, alginate-starch, and alginate-starch with chitosan coating as the wall materials. These microcapsules were characterized with regard to the morphology studied by using an optical microscope and scanning electron microscopy (SEM), particle size, and encapsulation efficiency. The microcapsules were then incorporated into the chewing gums. The chewing gums were characterized by thermal behavior (by differential scanning calorimetry [DSC]), texture profile analysis [TPA], and sensory evaluation. Furthermore, the release of caffeine from the chewing gum was studied in vitro using the masticatory simulator and in vivo by a chew-out study. The microcapsules revealed a spherical form and high encapsulation efficiency, representing the success of the technique. The outcomes indicated that it is possible to encapsulate caffeine with the techniques employed and the microcapsules prolonged the release of caffeine throughout mastication. The chewing gum containing alginate-starch with chitosan-coated microcapsules showed the great potential of the microcapsule in controlling the release of the caffeine from the chewing gum, thereby delaying its bitterness.     

Effect of Ionic Composition of Suspending Solution on Virus Adsorption by a Soil Column

The effect of various electrolytes on the adsorption of poliovirus was measured in 250-cm-long soil columns with ceramic samplers at different depths. Viruses suspended in deionized water moved much farther through the soil than those suspended in tap water, whereas movement in sewage water was intermediate. The salt content of the tap water and sewage water promoted virus adsorption, but evidently the organic compounds in sewage retarded adsorption. When viruses were suspended in chloride solutions of K⁺, Na⁺, Ca⁺, and Mg²⁺, virus adsorption increased as the cation concentration and valence increased. The depth of virus penetration was related to the ionic strength of the solutions. Virus penetration data for NO₃⁻, SO₄²⁻, and H₂PO₄⁻ salts of K⁺, Na⁺, and Ca²⁺ indicated that other anions were more effective than Cl⁻ in promoting virus adsorption. Also, NH₄⁺ was more effective than other cations in limiting the penetration depth of viruses. It seems that ions composed of radicals are more effective than ions composed of single atoms in promoting virus adsorption. Al³⁺ was the most effective ion in limiting virus penetration, probably owing to flocculation of the viruses. Adding AlCl₃ concentrations to secondary sewage effluent to provide an Al³⁺ concentration of 0.1 mM reduced the virus penetration depth to 40 cm. These studies show that the ionic composition of the suspending solutions must be considered in predicting virus penetration depths, and it may be practical to add low concentrations of a flocculating agent such as AlCl₃ to sewage water to limit virus movement through very porous soils.     

Vertebrates as a Bactericidal Agent

In Brazil, although a large number of animals are used in traditional medicine (at least 354 species), information about their biological activities is scarce. In this context, the objective of this study was to evaluate the bactericidal potential of zootherapeutic by-products from animals used in Brazilian traditional medicine and discuss the ecological and cultural consequences of such practices. The species analyzed were: Tupinambis merianae (skin), Iguana iguana (skin and body fat), Crotalus durissus (skin and body fat), Boa constrictor (skin), Euphractus sexcinctus (body fat) and Coendou prehensilis (quills). Experiments were performed with standard clinical strains of Escherichia coli (EC-ATCC10536) and Staphylococcus aureus (SA-ATCC 25923). For the microbiological assay, the zootherapeutics were evaluated using serial microdilutions. The results indicate that none of the samples possess inhibitory activity against standard bacterial strains. The in vitro ineffectiveness of the analyzed products demonstrate a necessity for new pharmacological research that encompass a large number of species of medicinal animals as well as highlight the importance of zootherapy in the context of plans for animal conservation.     

Dichloro-tetrafluoro-ethane as a Freezing Agent

Surgical skin planing is, in the hands of an experienced operator, a safe and highly effective procedure for treating a number of cutaneous defects, most notably pitted acne scars.The operation is facilitated by the use of a new instrument (jet-spray handpiece) which allows the operator to freeze the skin and plane it almost simultaneously, and by a new freezing agent, dichlorotetrafluoro-ethane, which adds to the safety by eliminating the old hazards of inflammability, explosion, and the toxic inhalation of ethyl chloride.The ability to sharply differentiate between keloid and hypertrophic scar is fundamental to surgical skin planing. A hypertrophic scar results from the removal or destruction of the cutaneous appendages (hair follicles, oil and sweat glands and ducts); whereas a keloid is an idiosyncratic response without regard to damage of the appendages.Properly performed surgical planing does not entirely remove these appendages and therefore healing occurs without scarring.     

Optimization Studies on Design and Evaluation of Orodispersible Pediatric Formulation of Indomethacin

In the present study, the aim was to optimize an orodispersible formulation of indomethacin using a combined approach of subliming agent and superdisintegrant. The tablets were made by non-aqueous wet granulation technique with superdisintegrant incorporated both intragranularly and extragranularly. A 2³ factorial design was used to investigate the effects amount of subliming agents namely camphor and ammonium bicarbonate and taste masking and soothening hydrophilic agent mannitol as independent variables and disintegration time and crushing strength as dependent responses. The volatilization time of eight hours at 50°C was optimized by conducting solid-state kinetic studies of optimized formulations. Optimized orodispersible tablets were evaluated for wetting time, water absorption ratio, porosity and in vitro and in vivo disintegration tests. Results show that higher levels of camphor and mannitol and a lower level of ammonium bicarbonate is desirable for orodispersion. Scanning electron microscopy (SEM) revealed the porous surface morphology and kinetic digital images substantiated the orodispersible property. Differential Scanning Calorimetry (DSC) studies exhibited physiochemical compatibility between indomethacin and various excipients used in the tablet formulation. Stability studies carried out as per ICH Q₁ A guidelines suggested the stable formulations for the tested time period of 6 months. The systematic approach of using subliming and disintegrating agents helped in achieving a stable, optimized orodispersible formulation, which could be industrially viable.     

Development of Oral Flexible Tablet (OFT) Formulation for Pediatric and Geriatric Patients: a Novel Age-Appropriate Formulation Platform

Development of palatable formulations for pediatric and geriatric patients involves various challenges. However, an innovative development with beneficial characteristics of marketed formulations in a single formulation platform was attempted. The goal of this research was to develop solid oral flexible tablets (OFTs) as a platform for pediatrics and geriatrics as oral delivery is the most convenient and widely used mode of drug administration. For this purpose, a flexible tablet formulation using cetirizine hydrochloride as model stability labile class 1 and 3 drug as per the Biopharmaceutical Classification System was developed. Betadex, Eudragit E100, and polacrilex resin were evaluated as taste masking agents. Development work focused on excipient selection, formulation processing, characterization methods, stability, and palatability testing. Formulation with a cetirizine-to-polacrilex ratio of 1:2 to 1:3 showed robust physical strength with friability of 0.1% (w/w), rapid in vitro dispersion within 30 s in 2–6 ml of water, and 0.2% of total organic and elemental impurities. Polacrilex resin formulation shows immediate drug release within 30 min in gastric media, better taste masking, and acceptable stability. Hence, it is concluded that ion exchange resins can be appropriately used to develop taste-masked, rapidly dispersible, and stable tablet formulations with tailored drug release suitable for pediatrics and geriatrics. Flexible formulations can be consumed as swallowable, orally disintegrating, chewable, and as dispersible tablets. Flexibility in dose administration would improve compliance in pediatrics and geriatrics. This drug development approach using ion exchange resins can be a platform for formulating solid oral flexible drug products with low to medium doses.     

Ibuprofen as a chemesthetic stimulus: evidence of a novel mechanism of throat irritation

This paper reports a study of the oral and pharyngeal chemesthetic effects of the non-steroidal anti-inflammatory drug (NSAID) ibuprofen [2-(4-isobutylphenyl)propanoic acid], which pilot experiments had indicated produces an unusual sensory irritation of the throat. In experiment 1 subjects swallowed aqueous solutions of ibuprofen prepared with different buffering agents and gave ratings of irritation and taste in the mouth and throat. The results showed that ibuprofen irritates the throat much more than the mouth, and that its quality in the throat is characterized primarily as sting/prick, itch and tickle (often leading to cough). Based upon the results obtained with the different buffering agents, we hypothesized that the sting/prick/itch qualities of throat irritation were pH-dependent. Parametric manipulation of solution pH in experiment 2 confirmed this hypothesis. The same experiment revealed that, in contrast to other oral irritants (e.g. capsaicin and menthol), repeated stimulation caused neither sensitization nor desensitization of throat irritation. In the final experiment we found that ibuprofen's throat irritation could not be modulated by temperature, as it should be if stimulation occurred via capsaicin-sensitive receptors. We therefore conclude that ibuprofen has novel chemesthetic properties, which are not mediated by capsaicin-sensitive (vanilloid) receptors, and that a major component of the throat irritation it produces occurs via a pH-dependent receptor mechanism.