Search Results (7)

Many pharmaceutical active compounds are prepared as hydrochlorides for quick release in the gastrointestinal tract upon oral administration. Their inadvertent escape into the water environment requires efficient analytical separation for accurate quantitation to monitor their environmental fate. The purpose of this study is to demonstrate how best to optimize a capillary electrophoresis method for the separation of four model pharmaceutical hydrochlorides. Concentration of sodium dibasic phosphate in the background electrolyte solution, pH adjustment with HCl or NaOH, and applied voltage across the capillary were the three key factors chosen for optimization. The peak resolutions and total migration time were examined as the response indicators to complete a central composite design in response surface methodology. The examination revealed that CE separation was driven significantly by a linear regression model and minimally by a quadratic regression model, based on the coefficient of determination, the lack of fit, the total sum of squares, and the p values. Under optimal conditions of the background electrolyte concentration of 75 mM, pH 9, and the applied voltage of 10 kV, the model hydrochlorides were separated within five minutes in the migration order of metformin (first) > phenformin > mexiletine > ranitidine (last). The limits of UV detection/quantification attained under optimal CE conditions were 0.015/0.045, 0.020/0.060, 0.142/0.426, and 0.017/0.051, respectively. Full article

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H₂ receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid^® 244FP and poloxamer^® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect. Full article

Here, we evaluate the feasibility of co-loading plain ranitidine hydrochloride (RHCl) and microencapsulated flurbiprofen (FBP) in a Lycoat^® RS780-based oral fast disintegrating film (ODF). These films were developed by the solvent casting method to minimize the adverse effects of FBP and reduce the dosage form burden on patients. Optimized FBP microparticles (M3) with an average size of 21.2 ± 9.2 µm were loaded alone (F1) and in combination with plain RHCl (F2) in the composite ODF. All films were evaluated physicomechanically and physicochemically. These films were resilient, flexible, and disintegrated within thirty seconds. SEM images showed intact FBP microparticles in both formulations and, moreover, did not observe an interaction between the drug and film components. Microencapsulated FBP was released in a controlled manner over 48 h from the proposed formulations, while RHCl was released within 5 min from F2. After in vitro evaluation, formulations were also tested for in vivo anti-inflammatory activity, cytokine (TNF-α and IL-6) levels, and gastroprotective effects in rats. The anti-inflammatory activity and gastroprotective effect of F2 were markedly higher than pure FBP and other synthesized formulations (M3 and F1). The average score of gastric lesions was in the order of pure FBP (15.5 ± 1.32) > M3 (8 ± 2) > F1 (1 ± 0.5) > F2 (0.5 ± 0) > control (0). Additionally, F2 showed a sustained anti-inflammatory effect up to 10 h in the rat paw edema model. Furthermore, F2 also markedly reduced TNF-α and IL-6 levels. Conclusively, the Lycoat^® RS780-based composite film could be a promising carrier for the co-loading of microencapsulated FBP with RHCl. In the future, an optimized formulation (F2) could be capable of countering the issues related to multiple drug administration in geriatric patients and evading the gastric irritation associated with FBP. Full article

Elevated levels of histamine cause over-secretion of gastric hydrochloric acid (HCl), leading to gastrointestinal (GI) disorders and anxiety. Ranitidine is an antihistamine drug widely used in the management of GI disorders, as it works by blocking the histamine−2 receptors in parietal cells, thereby reducing the production of HCl in the stomach. While some reports indicate the neuroprotective effects of ranitidine, its role against GI disorder-related anxiety remains unclear. Therefore, we investigated the effect of ranitidine against anxiety-related behaviors in association with changes in neuronal density in the hippocampal cornu ammonis (CA)–3 region of cysteamine hydrochloride-induced mouse model of GI disorder. Results obtained from the open field test (OFT), light and dark box test (LDBT), and elevated plus maze (EPM) test revealed that ranitidine treatment reduces anxiety-like behaviors in experimental animals. Nissl staining and immunohistochemical assessment of ionized calcium-binding adapter molecule (Iba)-1 positive microglia in cryosectioned brains indicated enhanced density of pyramidal neurons and reduced activation of microglia in the hippocampal CA–3 region of brains of ranitidine-treated experimental mice. Therefore, this study suggests that ranitidine mediates anxiolytic effects, which can be translated to establish a pharmacological regime to ameliorate anxiety-related symptoms in humans. Full article

Two metal oxide nanoparticles, magnesium oxide nanoparticles (MgONPs) and aluminum oxide nanoparticles (Al₂O₃NPs), were synthesized from green sources, Salvia officials and Cuminum cyminum seed extract, respectively. These nanoparticles were used for construction of potentiometric enhancement sensors employed for the estimation of ranitidine hydrochloride (RNT) in authentic powder and commercial products. The electroactive substance ranitidine-phosphotungstate (RNT-PT) was formed by combining RNT with phosphotungstic acid (PTA) in the presence of plasticizing material o-nitrophenyloctyl ether (o-NPOE). The outcomes showed that the enhanced MgO and Al₂O₃ nanosensors behaved linearly across the concentration ranges 1.0 × 10⁻⁹–1.0 × 10⁻² and 1.0 × 10⁻¹⁰–1.0 × 10⁻² mol L⁻¹, respectively. However, the conventional sensor (RNT-PT) displayed a linearity over 1.0 × 10⁻⁶–1.0 × 10⁻² mol L⁻¹. Least square equations were calculated as E_mV = (54.1 ± 0.5) log (RNT) + 762.33, E_mV = (58.6 ± 0.2) log (RNT) + 696.48, and E_mV = (52.2 ± 0.7) log (RNT) + 756.76 for enriched nanometal oxides modified and conventional sensors, respectively. The correlation coefficients of regression equations were 0.9997, 0.9995, and 0.9992 for the above suggested sensors, respectively. The recorded results showed excellent sensitivity and selectivity of the modified nanometal oxide sensors for the quantification of the analyzed drug in its authentic samples and commercial products. Full article

The purpose of the study was to develop a novel, directly compressible, co-processed excipient capable of providing a controlled-release drug system for the pharmaceutical industry. A co-processed powder was formed by adsorption of solid lipid nanoparticles (SLN) as a controlled-release film onto a functional excipient, in this case, dicalcium phosphate dihydrate (DPD), for direct compression (Di-Tab^®). The co-processed excipient has advantages: easy to implement; solvent-free; industrial scaling-up; good rheological and compressibility properties; and the capability to form an inert platform. Six different batches of Di-Tab^®:SLN weight ratios were prepared (4:0.6, 3:0.6, 2:0.6, 1:0.6, 0.5:0.6, and 0.25:0.6). BCS class III ranitidine hydrochloride was selected as a drug model to evaluate the mixture’s controlled-release capabilities. The co-processed excipients were characterized in terms of powder rheology and dissolution rate. The best Di-Tab^®:SLN ratio proved to be 2:0.6, as it showed high functionality with good flow and compressibility properties (Carr Index = 16 ± 1, Hausner Index = 1.19 ± 0.04). This ratio could control release for up to 8 h, so it fits the ideal profile calculated based on biopharmaceutical data. The compressed systems obtained using this powder mixture behave as a matrix platform in which Fickian diffusion governs the release. The Higuchi model can explain their behavior. Full article

A selective, specific and stability-indicating gradient reverse phase highperformance liquid chromatographic (HPLC) method was developed for the determination of Ranitidine in presence of its impurities, forced degradation products and placebo substances such as saccharide and parabens. Ultraviolet detection was performed at 230 nm. Separate portions of the drug product and ingredients were exposed to stress conditions to induce oxidative, acidic, basic, hydrolytic, thermal and photolytic degradation. Ranitidine was found to degrade significantly at acidic, basic and oxidative stress conditions but was stable at heat and humidity. The developed method was validated as per International Conference on Harmonization (ICH) guidelines. The method was validated over this range for (i) system suitability (ii) specificity, (iii) precision, (iv) limit of detection and limit of quantification, (v) linearity, (vi) accuracy, (vii) robustness. The method was found to be precise, accurate, linear and robust. The proposed method was successfully employed for estimation of Ranitidine impurities in pharmaceutical preparations. Full article