ENHANCEMENT OF LORNOXICAM SOLUBILITY BY INCLUSION COMPLEXATION WITH CYCLODEXTRIN: PREPARATION AND CHARACTERIZATION

Objective: Lornoxicam is a potent anti-inflammatory drug which has analgesic and antipyretic properties. It is water-insoluble powder. The inclusion complexes of lornoxicam (LOR) with β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (HPCD) were prepared and characterised in order to improve the solubility of the drug and enhance its bioavailability.Methods: Complexes were prepared by physical mixing and freeze-drying in three different drug/polymer ratios (1:1, 1:2 and 3:2). The solid complexes were characterised through differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray diffraction, nuclear magnetic resonance (NMR) spectroscopy, and Fourier transformed infrared (FTIR) spectroscopy.Results: The data showed that LOR may be complexed with cyclodextrin (CD) forming soluble complexes. The lyophilized 1:2 LOR/HPCD complex is the most soluble.Conclusion: Solubility increases with lyophilization than with physical mixing and by the use of HPCD than βCD in complexation

EFFECT OF BIODEGRADABLE CO-POLYMERS AND DIVALENT CATIONS ON THE SUSTAINED RELEASE ABILITY OF PROPRANOLOL HYDROCHLORIDE LOADED BIOMATERIAL MICROSPHERES

Objective: Propranolol Hydrochloride (PHCL) is used for the treatment of hypertension and angina pectoris; however it has two major problems; short biological halfâ€life and low bioavailability, so the aim of the present work was to develop PHCL mucoadhesive microsphere to prolong the residence time at the absorption site, therefore, increase the bioavailability.Methods: PHCL microspheres were prepared by ionotropic gelation method using nature polymers. Factorial design (33) was used to develop PHCL mucoadhesive microspheres, the independent factors used were polymer type (Sodium carboxymethyl cellulose (Na CMC), and Hydroxyl propyl methyl cellulose (HPMC), Carpobol 940), cross-linking type (calcium chloride, zinc chloride and barium chloride) and the concentration of Chitosan (0.5, 1, 1.5 %w/v). The developed microspheres were physicochemical characterized. The selected formula was selected for mucoadhesive test and in vivo study on human volunteers.Results: The results revealed that the PHCL mucoadhesive microspheres have good flowability, the mean particle sizes ranged from 541 to 815 µm and the entrapment efficiency ranged from 35.6% to 69.53%. The selected PHCL microspheres showed spherical particles with a rough surface and exhibited a slow release over 8h. The pharmacokinetic data of selected PHCL microspheres showed prolonged Tmax, decreased Cmax and AUC0–∞ value of 926.21±40.74ng. h/ml indicating improved relative bioavailability by144.93% compared with marketed tablets.Conclusion: PHCL microspheres were successfully prepared by ionic gelatin method that retards the release and enhances the oral bioavailability.Keywords: Propranolol HCL, Microspheres, Ionic gelation method, Chitosan, Relative bioavailabilit

Innovative pulmonary targeting of terbutaline sulfate-laded novasomes for non-invasive tackling of asthma: statistical optimization and comparative in vitro/in vivo evaluation.

Asthma represents a globally serious non-communicable ailment with significant public health outcomes for both pediatrics and adults triggering vast morbidity and fatality in critical cases. The β2-adrenoceptor agonist, terbutaline sulfate (TBN), is harnessed as a bronchodilator for monitoring asthma noising symptoms. Nevertheless, the hepatic first-pass metabolism correlated with TBN oral administration mitigates its clinical performance. Likewise, the regimens of inhaled TBN dosage forms restrict its exploitation. Consequently, this work is concerned with the assimilation of TBN into a novel non-phospholipid nanovesicular paradigm termed novasomes (NVS) for direct and effective TBN pulmonary targeting. TBN-NVS were tailored based on the thin film hydration method and Box-Behnken design was applied to statistically optimize the formulation variables. Also, the aerodynamic pattern of the optimal TBN-NVS was explored via cascade impaction. Moreover, comparative pharmacokinetic studies were conducted using a rat model. TBN elicited encapsulation efficiency as high as 70%. The optimized TBN-NVS formulation disclosed an average nano-size of 223.89 nm, ζ potential of −31.17 mV and a sustained drug release up to 24 h. Additionally, it manifested snowballed in vitro lung deposition behavior in cascade impactor with a fine particle fraction of 86.44%. In vivo histopathological studies verified safety of intratracheally-administered TBN-NVS. The pharmacokinetic studies divulged 3.88-fold accentuation in TBN bioavailability from the optimum TBN-NVS versus the oral TBN solution. Concisely, the results proposed that NVS are an auspicious nanovector for TBN pulmonary delivery with integral curbing of the disease owing to target specificity

NOVEL GASTRO-RETENTIVE POLYMERIC MICROSPHERES: AN APPROACH FOR INCREASED BIOAVAILABILITY AND AN ONCE DAILY DOSING OF TERBUTALINE SULPHATE

Objective: The purpose of this study was to develop multi-unit alginate-copolymer adhesive microspheres to achieve a sustained release of terbutaline sulphate (TBS) and overcome the hepatic first pass effect so as to enhance its bioavailability.Methods: The microspheres were prepared using inotropic gelation method and different concentration of sodium alginate alone or in combination with other polymers as well as using chitosan as a coating polymer in some formulations. All of the prepared microspheres were evaluated for yield, size, encapsulation efficiency, in vitro release and mucoadhesivity. The selected formulations (F11 and F19) were further subjected to differential scanning calorimetry, Fourier transform infrared spectroscopy, stability and in vivo bioavailability studies.Results: The prepared microspheres exhibited quite widely varying encapsulation efficiencies from 20 to 74. 8 % and its mean diameter was in range of 963. 3-1. 635 µm. The in vitro release study showed a sustained release profile. The selected formulations were further subjected to differential scanning calorimetry and FTIR which confirm the absence of any incompatibility. X-ray diffraction suggests the amorphous nature of the drug after encapsulation. The selected formulation F11 and F19 showing encapsulation efficiency higher than 55 %, an amount of drug released within 50-60 % after 8 h and a relative bioavailability of 283. 84 % and 202. 04 % respectively compared with the marketed oral Aironyl® tablets.Conclusion: The prepared microspheres were significantly efficient to achieve a sustained release of terbutaline sulphate with a higher relative bioavailability in comparison with the oral marketed tablet

Loratadine bioavailability via buccal transferosomal gel: formulation, statistical optimization, in vitro/in vivo characterization, and pharmacokinetics in human volunteers

Loratadine (LTD) is an antihistaminic drug that suffers limited solubility, poor oral bioavailability (owing to extensive first-pass metabolism), and highly variable oral absorption. This study was undertaken to develop and statistically optimize transfersomal gel for transbuccal delivery of LTD. Transfersomes bearing LTD were prepared by conventional thin film hydration method and optimized using sequential Quality-by-Design approach that involved Placket–Burman design for screening followed by constrained simplex-centroid design for optimization of a Tween-80/Span-60/Span-80 mixture. The transferosomes were characterized for entrapment efficiency, particle size, and shape. Optimized transferosomes were incorporated in a mucoadhesive gel. The gel was characterized for rheology, ex vivo permeation across chicken pouch buccal mucosa, in vitro release, and mucoadhesion. Pharmacokinetic behavior of LTD formulations was investigated in healthy volunteers following administration of a single 10-mg dose. Optimal transferosomes characterized by submicron size (380 nm), spherical shape and adequate loading capacity (60%) were obtained by using quasi-equal ratio surfactant mixture. In terms of amount permeated, percentage released, and mucoadhesion time, the transferosomal gel proved superior to control, transferosome-free gel. Bioavailability of the transferosomal gel was comparable to Claritin® oral tablets. However, inter-individual variability in Cmax and AUC was reduced by 76 and 90%, respectively, when the buccal gel was used. Linear Correlation of in vitro release with in vivo buccal absorption fractions was established with excellent correlation coefficient (R2>0.97). In summary, a novel buccal delivery system for LTD was developed. However, further clinical investigation is warranted to evaluate its therapeutic effectiveness and utility

Loratadine bioavailability via buccal transferosomal gel: formulation, statistical optimization, <i>in vitro</i>/<i>in vivo</i> characterization, and pharmacokinetics in human volunteers

<p>Loratadine (LTD) is an antihistaminic drug that suffers limited solubility, poor oral bioavailability (owing to extensive first-pass metabolism), and highly variable oral absorption. This study was undertaken to develop and statistically optimize transfersomal gel for transbuccal delivery of LTD. Transfersomes bearing LTD were prepared by conventional thin film hydration method and optimized using sequential Quality-by-Design approach that involved Placket–Burman design for screening followed by constrained simplex-centroid design for optimization of a Tween-80/Span-60/Span-80 mixture. The transferosomes were characterized for entrapment efficiency, particle size, and shape. Optimized transferosomes were incorporated in a mucoadhesive gel. The gel was characterized for rheology, <i>ex vivo</i> permeation across chicken pouch buccal mucosa, <i>in vitro</i> release, and mucoadhesion. Pharmacokinetic behavior of LTD formulations was investigated in healthy volunteers following administration of a single 10-mg dose. Optimal transferosomes characterized by submicron size (380 nm), spherical shape and adequate loading capacity (60%) were obtained by using quasi-equal ratio surfactant mixture. In terms of amount permeated, percentage released, and mucoadhesion time, the transferosomal gel proved superior to control, transferosome-free gel. Bioavailability of the transferosomal gel was comparable to Claritin® oral tablets. However, inter-individual variability in <i>C</i>_max and AUC was reduced by 76 and 90%, respectively, when the buccal gel was used. Linear Correlation of <i>in vitro</i> release with <i>in vivo</i> buccal absorption fractions was established with excellent correlation coefficient (<i>R²</i>>0.97). In summary, a novel buccal delivery system for LTD was developed. However, further clinical investigation is warranted to evaluate its therapeutic effectiveness and utility.</p

Repurposing celecoxib for colorectal cancer targeting via pH-triggered ultra-elastic nanovesicles: Pronounced efficacy through up-regulation of Wnt/β-catenin pathway in DMH-induced tumorigenesis

Celecoxib (CLX), a selective inhibitor for cyclooxygenase 2 (COX-2), has manifested potential activity against diverse types of cancer. However, low bioavailability and cardiovascular side effects remain the major challenges that limit its exploitation. In this work, we developed ultra-elastic nanovesicles (UENVs) with pH-triggered surface charge reversal traits that could efficiently deliver CLX to colorectal segments for snowballed tumor targeting. CLX-UENVs were fabricated via a thin-film hydration approach. The impact of formulation factors (Span 80, Tween 80, and sonication time) on the nanovesicular features was evaluated using Box–Behnken design, and the optimal formulation was computed. The optimum formulation was positively coated with polyethyleneimine (CLX-PEI-UENVs) and then coated with Eudragit S100 (CLX-ES-PEI-UENVs). The activity of the optimized nano-cargo was explored in 1,2-dimethylhydrazine-induced colorectal cancer in Wistar rats. Levels of COX-2, Wnt-2 and β-catenin were assessed in rats' colon. The diameter of the optimized CLX-ES-PEI-UENVs formulation was 253.62 nm, with a zeta potential of −23.24 mV, 85.64% entrapment, and 87.20% cumulative release (24 h). ES coating hindered the rapid release of CLX under acidic milieu (stomach and early small intestine) and showed extended release in the colon section. In colonic environments, the ES coating layer was removed due to high pH, and the charge on the nanovesicular corona was shifted from negative to positive. Besides, a pharmacokinetics study revealed that CLX-ES-PEI-UENVs had superior oral bioavailability by 2.13-fold compared with CLX suspension. Collectively, these findings implied that CLX-ES-PEI-UENVs could be a promising colorectal-targeted nanoplatform for effective tumor management through up-regulation of the Wnt/β-catenin pathway