Alternative Dosage Form Research Articles

Comparison of oven drying and freeze drying methods for the production of fast melt films containing quetiapine fumarate

Background Quetiapine fumarate (QTP) is commonly prescribed for schizophrenic patient, typically available in tablet or oral suspension form, presenting challenges such as administration difficulties, fear of choking and distaste for its bitter taste. Fast melt films (FMF) offer an alternative dosage form with a simple development process, ease of administration and rapid drug absorption and action onset. Objective This study aims to prepare FMF with different formulations using solvent casting methods and to compare the effects of different drying methods, including oven drying and freeze drying, on the properties of the films. Methods Various formulations were created by manipulating polymer types (starch, hydroxypropyl methylcellulose (HPMC) and guar gum) at different concentrations, along with fixed concentrations of QTP and other excipients. Characterisation tests including surface morphology, weight, thickness, pH, tensile strength, elongation length, Young’s modulus, folding endurance and disintegration time were conducted. The optimal FMF formulation was identified and further evaluated for moisture and drug content, dissolution behaviour, accelerated stability, X-ray diffraction (XRD), and palatability. Results FMF containing 10 mg guar gum/film developed using oven drying emerged as the optimum choice, exhibiting desirable film appearance, ultra-thin thickness (0.453 ± 0.002 mm), appropriate pH for oral intake (pH 5.0), optimal moisture content of 11.810%, rapid disintegration (52.67 ± 1.53 seconds), high flexibility (folding endurance > 300 times) and lower Young’s modulus (1.308 ± 0.214). Conclusion Oven drying method has been proven to be favourable for developing FMF containing QTP, meeting all testing criteria and providing an alternative option for QTP prescription.

The Effects of Different Dosages on Micronized Purified Flavonoid Fraction's Treatment of Lower Limb Chronic Venous Disease: A Meta-Analysis.

Micronized purified flavonoid fraction (MPFF) is a widely prescribed and extensively investigated venoactive drug (VAD). The standard dosage for MPFF is 500 mg administered twice daily. However, a new daily dose of 1000 mg has just been introduced. This study investigated whether a daily dose of 1000 mg MPFF could be implemented and embraced by the public and still has the same therapeutic effects as conventional pharmaceuticals. For this meta-analysis, we searched MEDLINE, Embase, Science of Web, Cochrane, and PubMed databases and forward and backward citations for studies published between database inception and March 2023. Three randomized controlled trials (RCTs) of comparison of different dosages of MPFF to evaluate whether there is a significant difference between them were included, without language or date restrictions. Due to the small sample size of the study included, we conducted a simple sensitivity test using a one-by-one exclusion method, and the results showed that the study did not affect the final consolidation conclusion. The quality of the evidence was assessed using the Cochrane risk-of-bias tool. Out of 232 studies, 99 were eligible and 39 RCTs had data, all with low to moderate bias. Overall, 1924 patients (experimental group: 967, control group: 957) in 3 RCTs met the criteria. There is no significant difference in patient compliance, efficacy, clinical adverse events, and quality of life scores between MPFF 1000 mg once daily and MPFF 500 mg twice daily (standardized mean difference [SMD]: 0.049 [0.048, 0.145], p=0.321, risk ratio [RR]: 0.981 [0.855, 1.125], p=0.904, and SMD: 0.063 [0.034, 0.160], p=0.203). In symptomatic chronic venous disease patients, MPFF 1000 mg once daily and MPFF 500 mg twice daily improve patient compliance, lower limb discomfort, clinical adverse events, and quality of life scores similarly. Regular medical care should recommend MPFF 1000 mg daily more often. Micronized purified flavonoid fraction (MPFF) is a popular venoactive medication (VAD) in modern medicine.MPFF is effective in treating lower extremity venous problems.Currently, besides conventional 500 mg tablets, there exist alternative dosage forms such as solutions, chewable tablets, and other novel formulations for MPFF.The excessive frequency and amount of medication may have a negative impact on patient adherence.

Advancing inflammatory skin disease therapy: Sustained tofacitinib release via electrospun fiber dressings

Inflammatory skin diseases are typically managed with semi-solid formulations such as creams and ointments. These treatments often fail to remain on the skin for long, as they can be easily wiped off by clothing, necessitating frequent reapplication throughout the day and resulting in poor patient adherence. Therefore, this study sought to fabricate an electrospun dressing as an alternative dosage form that provides a sustained release of the anti-inflammatory agent tofacitinib over three days. In this study, three types of electrospun fiber dressings – uniaxial, coaxial, and layer-by-layer – were produced and examined for their morphological, mechanical, and release characteristics. In addition to a comprehensive characterization, another objective was to analyze the drug permeation behavior from these fiber dressings on porcine skin, comparing their performance to that of a tofacitinib cream. The layer-by-layer system notably exhibited a delayed drug release, while the uniaxial and coaxial systems demonstrated an initial burst release. However, the permeation studies revealed no significant differences between these systems, underscoring the necessity of conducting such studies – a crucial aspect often overlooked in research on electrospun fiber dressings. Overall, this study highlights the potential of electrospun, drug-loaded dressings for the treatment of inflammatory skin diseases.

Thermo-activated in situ rectal gel preparation for Ibuprofen using eutectic mixture.

This study aimed to develop a thermosensitive in situ gel formulation for rectal delivery of Ibuprofen as an efficient alternative dosage form. Utilizing poloxamer 188, poloxamer 407, and HPMC via cold technique method, a thermosensitive in situ gel was successfully prepared. The concentration of Ibuprofen in the formulations was 1.2 % (w/w). The prepared gels underwent assessment for clarity, gelation temperature, gelation time, gel strength, spread ability, syringe-ability, pH, viscosity, FTIR, and drug content. The selected formulations exhibited a gelation temperature within the range of 30 °C to 36 °C, with consistent amount of drug soluble in the formulations (93 % - 110 %). Mucoadhesive studies, in vitro release tests, ex vivo modeling of drug release, kinetic studies modeling, and histopathology testing were also conducted. The formulation comprising 18 % poloxamer 407, 12 % poloxamer 188, and 1 % sodium chloride (FS15) demonstrated suitable gelation temperature and desirable drug release rate. In vitro drug release tests indicated completion within one hour for both FS10 (20 % P407 & 10 % P188) and FS15 (18 % P407 & 12 % P188), with consistent and predictable release patterns observed through kinetic modeling analysis. Microscopic histopathology examination confirmed the safety of the selected formula, exhibiting no irritation in the mucosal membrane of the sheep. In conclusion, Ibuprofen thermosensitive in situ gel presents a promising and convenient strategy as a rectal carrier and an alternative dosage form to solid suppositories.

The Development of Alternative Dosage Form for Creatine Monohydrate: A Floating Tablet

Creatine monohydrate has been developed as a neuroprotective agent and can penetrate in vitro model of the blood-brain barrier. However, its delivery is hampered by its limited capacity of creatine transporter. The floating system is known to increase the residence time of drugs in the stomach; thus, the active substances can be absorbed more optimally. Therefore, this study is aimed to develop creatine monohydrate floating tablets by optimizing the proportion of HPMC K100M and NaHCO2 and evaluating the quality of floating tablets. The formula was designed Simplex Lattice Design method. Tablets were prepared by the wet granulation method and evaluated for granule and tablet parameters. The results showed that HPMC K100M significantly increased flow time, absorption rate, hardness, floating time, swelling index; decreased index tap, fragility, and floating lag time. Meanwhile, an increase in NaHCO2 significantly affects an increase in floating lag time. The optimum formula obtained was 18.87% HPMC K100M and 21.12% NaHCO2. Verification of the optimum formula showed that tablet parameters were not significantly different from the predicted formula. The studies suggest that this prototype can be developed to increase creatine residence time in the stomach.

In Vitro and In Vivo Evaluation of Dark Chocolate as Age-appropriate Oral Matrix

Swallowing difficulties encountered by geriatric patients who undergo polypharmacy represent a significant challenge that hampers patient compliance and therapeutic management. As an appealing and sensory-pleasing, chocolate-based formulations have emerged as a potential alternative oral dosage form suitable for both the elderly and paediatric populations. However, the extent to which the incorporation of drugs into a chocolate matrix affects their oral availability remains unclear. Therefore, the objective of this investigation was to explore the in vitro and in vivo performance of an ibuprofen-based chocolate dosage form. A matrix based on dark chocolate and the model drug was prepared at two distinct temperatures: 50 and 80 °C. In vitro release studies revealed that ibuprofen formulated through co-melting at 80 °C exhibited a statistically significant slower drug release (p < 0.05) compared to formulations prepared at 50 °C in both FaSSGF (fasted-state simulated gastric fluid) and lipolysis media. The enzymatic degradation of chocolate in the presence of lipase accelerated in vitro ibuprofen release from chocolate matrices. To delve deeper into the bioavailability of ibuprofen within the chocolate formulations, we conducted an in vivo assessment, comparing the pharmacokinetic profiles of ibuprofen in its conventional suspension form with our chocolate-based dosage forms. A notable drop (p < 0.05) in the maximum serum concentration of ibuprofen when incorporated into co-melted or solid-suspension chocolate matrices. However, no significant differences in plasma exposure were observed between the two formulations. These findings shed a light on the potential of chocolate to extend of ibuprofen when integrated into various chocolate matrices, showcasing the potential held by these innovative formulations.

Management of Patients with Systemic Sclerosis-Associated Interstitial Lung Disease: A Focus on the Role of the Pharmacist.

Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc), which becomes fibrosing and progressive in some patients. Regular monitoring of patients with SSc-ILD is important to assess progression and inform treatment decisions. Therapy for SSc-ILD may include immunomodulatory and antifibrotic therapies. Therapeutic decisions should be made on a case-by-case basis, ideally following multidisciplinary discussion. Most patients with SSc-ILD have several organ manifestations of SSc or comorbidities and are taking a complex medication regimen. Patients with SSc are particularly susceptible to gastrointestinal side-effects of medications due to the gastrointestinal manifestations of the disease. Pharmacists play an important role in the management of patients with SSc-ILD by assisting patients with access to medications, optimizing medication regimens, and advising on alternative dosage forms. Pharmacists can also contribute to patient education to help patients better understand their treatment and how to prevent and manage potential side effects.

Influence of Solid Oral Dosage Form Characteristics on Swallowability, Visual Perception, and Handling in Older Adults.

Swallowability, visual perception, and any handling to be conducted prior to use are all influence factors on the acceptability of an oral dosage form by the patient. Knowing the dosage form preferences of older adults, as the major group of medication end users, is needed for patient-centric drug development. This study aimed at evaluating the ability of older adults to handle tablets as well as to assess the anticipated swallowability of tablets, capsules, and mini tablets based on visual perception. The randomized intervention study included 52 older adults (65 to 94 years) and 52 younger adults (19 to 36 years). Within the tested tablets, ranging from 125 mg up to 1000 mg in weight and being of different shapes, handling was not seen as the limiting factor for the decision on appropriate tablet size. However, the smallest sized tablets were rated worst. According to visual perception, the limit of acceptable tablet size was reached at around 250 mg for older adults. For younger adults, this limit was shifted to higher weights and was dependent on the tablet shape. Differences in anticipated swallowability with respect to tablet shapes were most pronounced for tablets of 500 mg and 750 mg in weight, independent of the age category. Capsules performed worse compared to tablets, while mini tablets appeared as a possible alternative dosage form to tablets of higher weight. Within the deglutition part of this study, swallowability capabilities of the same populations were assessed and have been reported previously. Comparing the present results with the swallowing capabilities of the same populations with respect to tablets, it shows adults' clear self-underestimation of their ability to swallow tablets independent of their age.

Hydroxypropyl methylcellulose orally disintegration films produced by tape casting with the incorporation of green propolis ethanolic extract using the printing technique

Green propolis ethanol extract (GPEE) is one of the most used compounds in folk medicine. Alternative dosage forms, such as orally disintegrating films (ODFs) and forms of incorporation of active principles, such as the printing technique, are arousing interest due to the possibility of producing personalized dosages and possible reduction of the degradation of compounds. The aim of this study was to evaluate the effect of green propolis ethanol extract (GPEE) incorporation on hydroxypropyl methylcellulose (HPMC) using the printing technique (1–4 print layers). GPEE was characterized by apparent viscosity, density, and surface tension. The ODFs with different numbers of printed layers were characterized in relation to color, moisture content, mechanical properties, structure, disintegration time, surface pH, stability, cytotoxicity, and anti-inflammatory activity tests. GPEE showed properties similar to those observed for commercial inks. The number of printed layers affected film properties. ODFs with GPEE showed anti-inflammatory activity, where a reduction of about 40% NO 2 − concentration against macrophage cells was found after adding one GPEE layer. As such, printing on hydroxypropyl methylcellulose oral films as a vehicle for green propolis ethanolic extract represents an interesting alternative to produce materials with controlled anti-inflammatory activity. • Viscosity, density and surface tension values of GPEE are similar to commercial inks. • Oral films of HPMC-based printed are a promising way to deliver active compounds. • HPMS-based printed films maintain the stability of phenolic compounds. • Films printed with green propolis ethanol extract have anti-inflammatory activity.

Development and Optimization of Imiquimod-Loaded Nanostructured Lipid Carriers Using a Hybrid Design of Experiments Approach.

Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara®) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option. Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach. The optimized formulation was then incorporated into a matrix-type topical patch as an alternative dosage form for topical application and evaluated for IMQ deposition across different skin layers in comparison to the performance of the commercial product. Additionally, our work also attempted to highlight the possibility of implementing environment-friendly practices in our IMQ-NLCs formulation development by reviewing our analytical methods and experimental designs and reducing energy and solvent consumption where possible. In this study, stearyl alcohol, oleic acid, Tween® 80 (polysorbate 80), and Gelucire® 50/13 (Stearoyl polyoxyl-32 glycerides) were selected for formulation development. The formulation was optimized using a 2k factorial design and a central composite design. The optimized formulation achieved the average particle size, polydispersity index, and zeta potential of 75.6 nm, 0.235, and - 30.9 mV, respectively. Subsequently, a matrix-type patch containing IMQ-NLCs was developed and achieved a statistically significant improvement in IMQ deposition in the deeper skin layers. The IMQ deposition from the patch into the dermis layer and receptor chamber was 3.3 ± 0.9 µg/cm2 and 12.3 ± 2.2 µg/cm2, while the commercial cream only deposited 1.0 ± 0.8 µg/cm2 and 1.5 ± 0.5 µg/cm2 of IMQ, respectively. In summary, IMQ-NLC-loaded patches represent great potential as a topical treatment option for skin cancer with improved patient compliance.

Formulation, evaluation and optimization of orally disintegrating films of Azithromycin using DOE approach for the pediatrics with acute otitis media

Acute otitis media (AOM) is a common infection of early childhood with an inflammation of the middle ear and tympanic membrane. Azithromycin is a macrolide antibiotic which is proficient to provide effective treatment for pediatric AOM due to its in-vitro activity against the most common upper respiratory tract pathogens. The objective of this study was to develop and optimize orally disintegrating films (ODF) of azithromycin as an alternative patient compliant dosage form. Using casting method of films, five formulations (F1-F5) were fabricated and evaluated for different physico-chemical and mechanical parameters along with drug release kinetics. Design of Experiment approach was applied to discover the optimized ratio of the two disintegrants used in the formulations. FT-IR spectra confirmed the identity of azithromycin and absence of any chemical interaction between the drug and excipients. Optimized formulation was selected as F2 which comprised of two disintegrants i.e. crospovidone and croscarmellose sodium in 1:1 ratio. F2 possessed excellent physico-chemical, mechanical properties along with rapid dissolution. F2 demonstrated concentration dependent erosional type release pattern from a planer surface of hydrophilic matrix system. Addition of the disintegrating agents resulted in rapid fragmentation of the films following the above process. Accelerated stability study assured the longer shelf life of optimized ODFs. Rapid disintegration and dissolution may accelerate the onset of action bypassing hepatic first-pass metabolism which confirmed the utility of azithromycin loaded ODFs as alternative dosage form in management of pediatric AOM.

FORMULATION AND EVALUATION OF IMPLANTABLE DRUG DELIVERY OF DISULFIRAM

Disulfiram is widely prescribed to discourage alcoholics from drinking alcohol. The effectiveness of oral disulfiram as a treatment for alcoholism is severely limited due to its poor bioavailability and poor patient compliance. To minimize the failure of the orally administered drug, efforts have been made to prepare alternative dosage form of subcutaneously implantable disulfiram pellets or tablets. In the present study an attempt has been made to design and evaluate a disulfiram implant using plain drug. The disulfiram implants have been formulated by direct compression and the effect of parameters like pH of site of administration (6.0 and 7.4) and sterilization were studied on in-vitro release of implantable disulfiram pellets. In- vitro release has been studied by vial and rotary flask shaker methods. The release kinetic mechanism from all the formulation was found to be zero order. The in vitro release data of all the formulations was compared with that of marketed disulfiram implant (Esperal). In contrast to other formulation in vitro release from marketed formulation appeared to be independent of hydrodynamics of diffusion (volume of dissolution media and agitation speed). The present study had revealed that, in-vitro drug release from implants is unaffected by pH of site of administration and gamma ray sterilization. Both the methods (Vial Method &amp; Rotating Flask Method) of in vitro dissolution testing are found significantly different for formulations prepared in laboratory but not for marketed formulation, indicating the different mechanism of release of marketed formulation.

MINIMAL IMPACT OF FOOD, DRINK, OR TEMPERATURE ON THE PHARMACOKINETICS OF A SUBLINGUAL FILM USING AA NOVEL PRODRUG OF EPINEPHRINE (DESF)

<h3>Introduction</h3> DESF is a novel alternative dosage form to Epinephrine injection. A pre-clinical study was conducted to test the effect of sublingual temperature (SL) and if exposure of the sublingual mucosa to food or drink prior to administration of DESF has an impact on the PK profile of epinephrine <i>in vivo</i>. <h3>Methods</h3> A total of 18 male Yucatan miniature swine, separated into three groups and dosed with DESF 12 mg, were used for this study. Group 1 did not receive a pre-treatment. Groups 2 and 3 were pretreated with either full-fat whole milk or extra virgin olive oil or with either warm or cool compresses at the dose site. Following dosage, the animals had Pharmacokinetics (PK) blood samples obtained at multiple timepoints, with Oral Mucositis Assessment Scale scores performed at pre-dose, 4-, and 24-hours post-dose. <h3>Results</h3> Similar PK profiles were observed for epinephrine regardless of pretreatment of food and drink. Groups pretreated with milk or oil displayed a mean Cmax and AUC similar to or higher than the control group. Tmax was similar for all treatment groups, between 25 to 30 minutes. As for the impact of temperature, pre-treatment with a warm or cool compress did not result in significantly different SL temperatures. Similar PK profiles were also observed for epinephrine regardless of pre-treatment. Simple linear regression analysis suggests that there was not a strong relationship between SL temperature and Cmax. <h3>Conclusion</h3> These results suggest that food, drink, and temperature each have minimal impact on the PK profiles of DESF.

Nanoformulation of Seaweed Eisenia bicyclis in Albumin Nanoparticles Targeting Cardiovascular Diseases: In Vitro and In Vivo Evaluation.

Natural products, especially those derived from seaweeds, are starting to be seen as effective against various diseases, such as cardiovascular diseases (CVDs). This study aimed to design a novel oral formulation of bovine albumin serum nanoparticles (BSA NPs) loaded with an extract of Eisenia bicyclis and to validate its beneficial health effects, particularly targeting hypercholesterolemia and CVD prevention. Small and well-defined BSA NPs loaded with Eisenia bicyclis extract were successfully prepared exhibiting high encapsulation efficiency. Antioxidant activity and cholesterol biosynthesis enzyme 3-hydroxy-3 methylutaryl coenzyme A reductase (HMGR) inhibition, as well as reduction of cholesterol permeation in intestinal lining model cells, were assessed for the extract both in free and nanoformulated forms. The nanoformulation was more efficient than the free extract, particularly in terms of HMGR inhibition and cholesterol permeation reduction. In vitro cytotoxicity and in vivo assays in Wistar rats were performed to evaluate its safety and overall effects on metabolism. The results demonstrated that the Eisenia bicyclis extract and BSA NPs were not cytotoxic against human intestinal Caco-2 and liver HepG2 cells and were also safe after oral administration in the rat model. In addition, an innovative approach was adopted to compare the metabolomic profile of the serum from the animals involved in the in vivo assay, which showed the extract and nanoformulation’s impact on CVD-associated key metabolites. Altogether, these preliminary results revealed that the seaweed extract and the nanoformulation may constitute an alternative natural dosage form which is safe and simple to produce, capable of reducing cholesterol levels, and consequently helpful in preventing hypercholesterolemia, the main risk factor of CVDs.

Review on Orodispersible Tablet: Recent Trends of Manufacturing of Orodispersible Tablet

The article mainly focuses on several aspects of orodispersible tablets (ODTs). These types of tablets are those when placed in the mouth cavity disperse the drug in very rapid manner i.e. instantaneously releasing the drug which dissolve in saliva. ODTs are alternative dosage forms for the patients who are suffering from dysphasia i.e. difficulty in swallowing. The oral administration of the drug is most important method for administrating the drugs for systemic effects. Except that the parenteral route is not used routinely for self-administration e.g. insulin. The topical route is only applicable to deliver the drugs into the body for the systemic effect. The administration of the drug by the parenteral route is only beneficial for treating medical emergencies in which the subject is comatose or can’t swallow. Never the less it is probable that at least 90% of all drugs used to provide systemic effects are administered by the oral route. ODTs are different from traditional tablets in that they are designed to be dispersed on the tongue rather than swallowed whole. ODTs dissolve or disintegrate in the oral cavity without the need of water or chewing. And also it is mainly used for rapid action, to enhance the bioavailability, accurate dosing, enhance palatability, ease of administration, accurate dosing, having good patient compliance because most of the people are familiar with this route. Drugs present in ODTs do not suffer from the first-pass metabolism. This type of drug administration or delivery is becoming popular day by day due to its numerous advantages.

Rational Dispensing of Oral Dosage Forms of Medicines to Children and Its Associated Factors in South West Ethiopia.

IntroductionObstacles encountered when maintaining excellent dispensing practices for children include a lack of age-appropriate dosage forms, a shortage of medications in appropriate strengths for children, a lack of appetizing drugs, and a lack of competence in pediatric pharmacy. These difficulties contribute to ineffective dispensing procedures and an urgent need to study whether oral dose forms of medications are dispensed to children in a rational way.ObjectiveThe purpose of this study is to evaluate the rational dispensing of oral dosage forms of medicines to children, as well as the factors that influence this practice.MethodsUsing validated indicators, a cross-sectional study design was utilized to analyze the rational dispensing practice of oral dosage forms of medicines administered to children under the age of 12 years in seven pharmacies and two drug stores over a one-month period.Results and discussionsOut of 810 medicines, 11.7% and 4% were irrationally manipulated, 5.8% and 1.8% needed manipulation, 3.7% and 0.2% were alternatively dispensed, 8.8% and 7.5% of the medicines had correct advice on their label and also 745 medicines were adequately labeled in the hospital and the selected drug stores. In this study, 92% of medicines were adequately labeled and had sufficient advice on their labels, 15.3% of medicines were irrationally manipulated and around 7.7% of the dosage forms needed manipulation during dispensing. The type of medicine retail outlet had a significant effect on the percentage of instances where alternative solid oral dosage forms were dispensed (p = 0.003), the percentage of dosage forms were adequately labeled (p = 0.008), and the percentage of dosage forms were irrationally manipulated before dispensing (p = 0.001).ConclusionThe rational dispensing practice of oral dosage forms of medicines was relatively poor and there is room for improvement.

EFFECT OF HYDROPHILIC POLYMER ON DESIGN EXPERT ASSISTED ORO-DISPERSIBLE STRIP (ODS) OF ISOSORBIDE MONONITRATE

Oral conventional formulations like tablets, capsules and liquids have many limitations. Due to this and patient incompliance, there is a need to develop new formulations with better efficiency and stability. The aim of the present study was to develop and optimize fast dissolving Oro-dispersible strips (ODS) of isosorbide mononitrate by 32 -full factorial design. HPMC E15 (X1 ) concentration and glycerin (X2 ) concentration were selected as the independent variables, whereas, in vitro disintegration time (Y1 ), percent drug release (Y2 ) and tensile strength (Y3 ) were selected as dependent variables. Fast dissolving Oro-dispersible strips of isosorbide mononitrate were prepared by the solvent casting method.Tensile strength, disintegration time and in vitro dissolution of ODS of the strip were found to be within accepted range for optimized formulation. Statistical validity of the polynomials was established by ANOVA using Design-Expert software. The study suggests isosorbide mononitrate fast dissolving Oro-dispersible strip as potential alternative dosage form in management of angina pectoris.

Formulation Design and Cell Cytotoxicity of Curcumin-Loaded Liposomal Solid Gels for Anti-Hepatitis C Virus.

Backgrounds Curcumin (CUR) is a low-molecular-weight polyphenolic substance obtained from the tuber part of Curcuma species. Anti-inflammatory and anti-hepatitis C virus (HCV) activities have been associated with CUR. However, its poor aqueous solubility and low systemic bioavailability have been the challenges in improving the therapeutic efficacy of curcumin. Aim The study aimed to produce CUR-loaded liposomal solid gels as anti-HCV delivery systems. Parameters including the physical characteristics and the cell cytotoxicity properties were evaluated. Methods The freeze-drying technique was applied to manufacture the CUR-loaded liposomal solid gels. Scanning electron microscopy (SEM), X-ray diffractometry (XRD), and differential thermal analysis (DTA) were involved to reveal the characteristics of the solid gels. Such characteristics were as follows: the morphology and the microscopic structure of the solid gels, the crystallinity structure of the curcumin, and the thermal properties of the mixtures. Furthermore, their cell cytotoxicity was investigated using a Huh7it cell line. Results The SEM images confirmed that curcumin liposomes were intact and trapped in the solid gel matrix. The XRD data showed flat patterns diffractograms of the formulations, confirming the transformation of CUR from crystalline to amorphous form. The DTA thermograms showed a single melting endothermic peak at a higher temperature around 200°C, indicating a single-phase transition of the mixtures. The XRD and DTA data revealed the molecular dispersion of CUR in the developed formulations. The cytotoxicity data provided as cell cytotoxicity 50 (CC50) for all formulations were ≥25 mg. These data confirmed that the developed liposomal solid gels were not cytotoxic to Huh7it cell line, indicating that the anti-HCV activity would be through a specific pathway and not by its toxicity. Conclusion The CUR-loaded liposomal solid gels exhibited the potential and offered an alternative dosage form to improve the therapeutic efficacy of curcumin as an anti-HCV.

Formulation development, optimization by Box-Behnken design, characterization, in vitro, ex-vivo, and in vivo evaluation of bosentan-loaded self-nanoemulsifying drug delivery system: A novel alternative dosage form for pulmonary arterial hypertension treatment

This study aimed to develop and optimize a self-nanoemulsifying drug delivery system (SNEDDS) of bosentan (BOS) to solve its poor oral bioavailability due to low water solubility. A pseudo-ternary phase diagram was created based on the solubility and emulsification studies. The major components of the formulation were selected as glyceryl monolinoleate (lipid), polyoxyl 40 hydrogenated castor oil (surfactant), and caprylocaproyl polyoxyl-8 glycerides (co-surfactant). The composition of BOS-SNEDDS was optimized using the Box-Behnken design (BBD) and then was characterized for various physicochemical properties. The in vitro dissolution, in vitro lipolysis, and ex-vivo permeability studies were performed and compared to SNEDDS and reference tablets. The fasted and fed state bioavailability of BOS-loaded SNEDDS was evaluated in Wistar rats (n = 6) compared to the reference. The prepared SNEDDS were thermodynamically stable with a droplet size of 17.11 nm, a polydispersity index of 0.180, and an emulsification time of <1 min. The BOS-loaded SNEDDS showed 3.0, 7.97, 4.23, and 4.94-fold increases in the percentages of cumulative dissolution compared to reference tablets in FaSSIF, FeSSIF, FaSSIF-V2, and FeSSIF-V2, respectively. The permeation study showed that the SNEDDS increased the drug permeation by 3.36, 19.2, 16.4, and 16.6-fold in FaSSIF, FeSSIF, FaSSIF-V2, and FeSSIF-V2, respectively. The enhancement of in vitro dissolution, in vitro lipolysis, and ex-vivo permeability was found significant (p < 0.05). SNEDDS was increased the Cmax and AUC 1.67 and 2.12-fold and 5.15 and 1.84-fold in fasted and fed state compared to the reference, respectively. The in vitro-in vivo relationship has been successfully performed for SNEDDS. These results indicated that the SNEDDS formulation could be a promising delivery system that enhances the absorption and oral bioavailability of BOS.

CHARACTERISTICS AND STABILITY OF IBUPROFEN MICROEMULSION PER INJECTION USING A COMBINATION OF MEDIUM-CHAIN TRIGLYCERIDE OIL, EXTRA VIRGIN OLIVE OIL, AND VIRGIN COCONUT OIL AS THE OIL PHASE

Injectable ibuprofen has been formulated as nanoemulsion, prodrug microemulsion, and freeze-dried. However, its application is limited because of solubility, high dosing, and complex formulation. Microemulsion ibuprofen injection is an alternative dosage form that increases solubility and bioavailability. The study aimed to formulate an ibuprofen microemulsion injection that can fulfill the prerequisites for injection preparations with a simple method and simple reconstitution before use. All combinations of the oil and aqueous phases were formed using the self-emulsification technique. The optimum stability was estimated on particle size, polydispersity index (PDI), and zeta potential at 5°C, 25°C, and 40°C for 120 days. Based on the minimum amount of Tween 80, drug loading, and the highest transmittance value, the optimal microemulsion formula was obtained at a concentration of 2.8% (1:1 combination of olive oil and medium-chain triglyceride oil), 11.2% Tween 80, 2.8% propylene glycol, and 83.2% water for injection. The optimal formula has a droplet size of 16.7 ± 11.2 nm, a zeta potential of 0.8 mV, and a PDI of 0.196. The formula was stable at 45°C storage for up to 14 days, at 25°C, and at 5°C, steady at 120 days based on droplet size diameter of 21.27 ± 0.00 nm, zeta potential -1.3 ± 0.10 mV, and PDI 0.38 ± 0.02. The optimum formula by simple reconstitution without additional isotonization has fulfilled the requirements for injection preparation. It was concluded that the ibuprofen microemulsion with a combination of medium-chain triglyceride oil and olive oil could form a stable microemulsion and has the potential to be developed as a pharmaceutical preparation in the form of injectable ibuprofen.