Mona Hassan Aburahma

Novel diphenyl dimethyl bicarboxylate provesicular powders with enhanced hepatocurative activity: Preparation, optimization, in vitro/in vivo evaluation

Diphenyl dimethyl bicarboxylate (DDB) is a hepatocurative agent used for treatment of various liver diseases. However, DDB therapeutic effectiveness is restricted by its low oral bioavailability that arises from its poor solubility and dissolution. Aiming at surmounting the aforementioned restrictions, DDB provesicular dry powders exemplified by proniosomes and proliposomes were prepared using film-deposition technique employing sorbitol as a carrier. Upon dilution with water, the provesicular powders rapidly transformed into vesicular dispersions, either liposomes or niosomes, which were characterized regarding their percent encapsulation efficiency (EE%), vesicle size and distribution, morphology and in vitro drug release. The revealed optimal provesicular powder was exposed to solid state characterization, stability testing and in vivo performance evaluation. Results showed that provesicular powders with acceptable flowability can be prepared using a weight ratio of lipids mixture to sorbitol of 1:20. Proniosomal powder composed of Tween 80:cholesterol:stearylamine in molar ratio 7:3:0.5 loaded on sorbitol was selected as the optimal formulation as it showed the highest EE% and dissolution enhancement for DDB. The elevated levels of liver enzymes in hepatically injured Albino Wister rats were significantly reduced (P<0.05) after oral administration of the optimal proniosomal powder in comparison to free DDB. This improvement was confirmed histopathologically by minimizing the associated hepatic injury. Accordingly, proniosomes can be assertively considered as a promising stable precursor for immediate preparation of niosomal carrier for DDB with enhanced dissolution and hepatocurative activity.

Compritol 888 ATO: a multifunctional lipid excipient in drug delivery systems and nanopharmaceuticals

Introduction: Compritol® 888 ATO is a lipid excipient that is generally used in cosmetic industry as a surfactant, emulsifying agent and viscosity-inducing agent in emulsions or creams. Based on its chemical composition, Compritol 888 ATO is a blend of different esters of behenic acid with glycerol. Areas covered: Recently, there has been great interest in the multiple roles that Compritol 888 ATO plays in various pharmaceutical delivery systems. Accordingly, this review aimed at summarizing the current and potential applications of Compritol 888 ATO in various drug delivery areas. Expert opinion: Different researches have highlighted the feasibility of using Compritol 888 ATO as a lubricant or coating agent for oral solid dosage formulations. It has also been explored as a matrix-forming agent for controlling drug release. At present, the most common pharmaceutical application of Compritol 888 ATO is in lipid-based colloidal drug delivery system such as solid lipid microparticles, solid lipid nanoparticles and nanostructured lipid carriers. Although, Compritol 888 ATO has acceptable regulatory and safety profiles and although the number of articles that emphasize on its applicability as an innovative excipient in pharmaceutical technology is continuously increasing, it is not widely used in the pharmaceutical market products and its use is limited to its sustain release ability in extended release tablets.

Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines

Abstract Most of the new drugs, biological therapeutics (proteins/peptides) and vaccines have poor performance after oral administration due to poor solubility or degradation in the gastrointestinal tract (GIT). Though, vesicular carriers exemplified by liposomes or niosomes can protect the entrapped agent to a certain extent from degradation. Nevertheless, the harsh GIT environment exemplified by low pH, presence of bile salts and enzymes limits their capabilities by destabilizing them. In response to that, more resistant bile salts-containing vesicles (BS-vesicles) were developed by inclusion of bile salts into lipid bilayers constructs. The effectiveness of orally administrated BS-vesicles in improving the performance of vesicles has been demonstrated in researches. Yet, these attempts did not gain considerable attention. This is the first review that provides a comprehensive overview of utilizing BS-vesicles as a promising pharmaceutical carrier with a special focus on their successful applications in oral delivery of therapeutic macromolecules and vaccines. Insights on the possible mechanisms by which BS-vesicles improve the oral bioavailability of the encapsulated drug or immunological response of entrapped vaccine are explained. In addition, methods adopted to prepare and characterize BS-vesicles are described. Finally, the gap in the scientific researches tackling BS-vesicles that needs to be addressed is highlighted.

Investigating the potential of employing bilosomes as a novel vesicular carrier for transdermal delivery of tenoxicam.

Bilosomes represent an evolving vesicular carrier that have been explored for oral vaccines delivery based on its ability to resist enzymes and bile salts in the gastrointestinal tract (GIT). Bilosomes vesicles are formed of bilayer membrane of non-ionic surfactant molecules encompassing bile salts. Although, bilosomes have not been proposed for transdermal drug delivery, this carrier seems to have promising potential in this regard. Accordingly, the aim of this investigation was to assess the capability and safety of utilizing bilosomes for transdermal delivery of tenoxicam (TX) as a model drug. A 3(1)2(2) full factorial design was adopted to study the effects of different formulation parameters on bilosomes properties and select the optimal formulation using Design-Expert(®) software. The selected formulation displayed nano-sized spherical vesicles (242.5 ± 6.43nm) with reasonable entrapment efficiency percent (68.33 ± 2.33%). Confocal laser scanning microscopy confirmed the capability of the flourolabeled bilosomes to penetrate deep within the skin. Both, ex vivo permeation and in vivo skin deposition studies confirmed the superiority of bilosomes over drug solution in delivering TX transdermally. In addition, in vivo histopathological study proved the safety of topically applied bilosomes. In summary, the highlighted results confirmed that bilosomes can be further adopted for delivering drugs transdermally.

Innovation of novel sustained release compression-coated tablets for lornoxicam: formulation and in vitro investigations.

OBJECTIVE The objective of this study was to modify the release characteristics of lornoxicam, a highly potent nonsteroidal anti-inflammatory drug, by preparing compression-coated tablets (CCTs) that provide complete drug release that starts in the stomach to rapidly alleviate the painful symptoms and continues in the intestine to maintain prolonged analgesic effect as well as meets the reported sustained release specifications. METHODS Each of the prepared CCTs was composed of a sustained release tablet core and an immediate release coat layer. Amorphous, well-characterized, freeze-dried solid dispersion of lornoxicam with polyvinylpyrrolidone K-30 was employed in the coat layer to attain an initial rapid dissolution of lornoxicam in the stomach, assuring rapid onset of analgesic effect. Compritol ATO 888, a lipophilic matrix-forming material, was included in the core tablets to sustain lornoxicam release. Lactose was also incorporated into these core tablets to ensure complete release of lornoxicam in a time period comparable to the gastrointestinal residence time. RESULTS All the prepared CCTs showed acceptable physical properties that complied with compendial requirements. On the basis of in vitro drug release studies, performed in simulated gastric and intestinal fluids in sequence to mimic the gastrointestinal transit, CCTs belonging to formulations F3 CCTs and F4 CCTs were able to show the desired release profile. CONCLUSION This study demonstrated the possibility of modulating lornoxicam release using CCTs to meet the reported sustained release specifications.

Ufasomes nano-vesicles-based lyophilized platforms for intranasal delivery of cinnarizine: preparation, optimization, ex-vivo histopathological safety assessment and mucosal confocal imaging

Abstract To circumvent the low and erratic absorption of orally administrated cinnarizine (CN), intranasal lyophilized gels containing unsaturated fatty acid liposomes (ufasomes) and encapsulating CN were prepared from oleic acid using a simple assembling strategy. The effects of varying drug concentration and cholesterol percentage on ufasomes size, polydispersity index and entrapment efficiency were investigated using 3141 full factorial design. The optimized ufasomes that contained 14% cholesterol relative to oleic acid displayed spherical morphology with average size of 788 nm and entrapment efficiency of 80.49%. To overcome the colloidal instability of CN-loaded ufasomes dispersions and their short residence time in the nasal cavity, the ufasomes were incorporated into mucoadhesive hydrogels that were lyophilized into unit dosage forms for accurate dosing. Scanning electron micrographs of the lyophilized gel revealed that the included ufasomes were intact, non-aggregating and maintained their spherical morphology. Rheological characterization of reconstituted ufasomal lyophilized gel ensured ease of application. Furthermore, the gel induced minor histopathological alterations in sheeps’ nasal mucosa. Ex-vivo confocal laser imaging confirmed the ability of ufasomes to penetrate deep through nasal mucosa layers. The results highlighted in the current work confirm the feasibility of using CN-loaded ufasomal gels for intranasal drug delivery.

Preparation and In Vitro/In Vivo Characterization of Porous Sublingual Tablets Containing Ternary Kneaded Solid System of Vinpocetine with β-Cyclodextrin and Hydroxy Acid

The demand for sublingual tablets has been growing during the previous decades especially for drugs with extensive hepatic first-pass metabolism. Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor aqueous solubility and marked first-pass metabolism. Accordingly, the aim of this work was to develop tablets for the sublingual delivery of vinpocetine. Initially, the feasibility of improving vinpocetine’s poor aqueous solubility by preparing kneaded solid systems of the drug with β-Cyclodextrin and hydroxy acids (citric acid and tartaric acid) was assessed. The solid system with improved solubility and dissolution properties was incorporated into porous tablets that rapidly disintegrate permitting fast release of vinpocetine into the sublingual cavity. The pores were induced into these tablets by directly compressing the tablets’ excipients with a sublimable material, either camphor or menthol, which was eventually sublimated leaving pores. The obtained results demonstrated that the tablets prepared using camphor attained sufficient mechanical strength for practical use together with rapid disintegration and dissolution. In vivo absorption study performed in rabbits indicated that the sublingual administration of the proposed porous tablets containing vinpocetine solid system with β-Cyclodextrin and tartaric acid could be useful for therapeutic application.

Educational Games as a Teaching Tool in Pharmacy Curriculum

The shift in the pharmacist’s role from simply dispensing medications to effective delivery of pharmaceutical care interventions and drug therapy management has influenced pharmacy education.1-3 The educational focus has shifted from basic sciences to clinical and integrated courses that require incorporating active-learning strategies to provide pharmacy graduates with higher levels of competencies and specialized skills. As opposed to passive didactic lectures, active-learning strategies address the educational content in an interactive learning environment to develop interpersonal, communication, and problem-solving skills needed by pharmacists to function effectively in their new roles.4-6 One such strategy is using educational games. The aim of this paper is to review educational games adopted in different pharmacy schools and to aid educators in replicating the successfully implemented games and overcoming deficiencies in educational games. This review also highlights the main pitfalls within this research area.

Oro-dental mucoadhesive proniosomal gel formulation loaded with lornoxicam for management of dental pain

Abstract Oro-dental diseases are generally associated with pain that is controlled using oral tablets containing NSAIDs. Lornoxicam, a relatively new NSAID, is effective in relieving pain accompanying different oro-dental problems. The aim of the current research is to prepare oro-dental analgesic and anti-inflammatory gel using provesicular approach to deliver lornoxicam directly to the site of action in the oral cavity. Local administration of lornoxicam is expected to be superior to systemic delivery in pain relieving and poses less GIT adverse effects. Different surfactants were utilized to prepare the proniosomal gels that rapidly transform into nano-sized niosomes after hydration with the oral saliva. The effect of the surfactant structure on vesicles size distribution and entrapment efficiency percentage (EE%) was investigated. The proniosomal formulations were incorporated into carbopol hydrogels that were characterized regarding rheological and mucoadhesion properties. Moreover, ex-vivo mucosal membrane permeation studies were conducted for selected proniosomal gels to quantify the permeation parameters and assess the amount of drug deposited within the oral mucosa. Results revealed that mucoadhesive proniosomes formulation prepared using Span 60 was optimal as it was nano-sized and also showed the highest EE%. The transmucosal flux of lornoxicam, from these proniosomal formulations, across the oral mucosa was significantly higher (p < 0.05) than lornoxicam containing carbopol gel and the percent drug diffused increased more than twofolds. The results collectively suggest that the mucoadhesive proniosomal gels can be assertively considered as a promising carrier for transmucosal delivery of lornoxicam into the oral cavity.

Design and in vitro evaluation of novel sustained-release matrix tablets for lornoxicam based on the combination of hydrophilic matrix formers and basic pH-modifiers

The short half-life of lornoxicam, a potent non-steroidal anti-inflammatory drug, makes the development of sustained-release (SR) forms extremely advantageous. However, due to its weak acidic nature, its release from SR delivery systems is limited to the lower gastrointestinal tract which consequently leads to a delayed onset of its analgesic action. Accordingly, the aim of this study was to develop lornoxicam SR matrix tablets that provide complete drug release that starts in the stomach to rapidly alleviate the painful symptoms and continues in the intestine to maintain protracted analgesic effect as well as meets the reported SR specifications. The proposed strategy was based on preparing directly compressed hydroxypropylmethylcellulose matrix tablets to sustain lornoxicam release. Basic pH-modifiers, either sodium bicarbonate or magnesium oxide, were incorporated into these matrix tablets to create basic micro-environmental pH inside the tablets favorable to drug release in acidic conditions. All the prepared matrix tablets containing basic pH-modifiers showed acceptable physical properties before and after storage. Release studies, performed in simulated gastric and intestinal fluids used in sequence to mimic the GI transit, demonstrate the possibility of sustaining lornoxicam release by combining hydrophilic matrix formers and basic pH-Modifiers to prepare tablets that meet the reported sustained-release specifications.