Pharmacotechnical and analytical preformulation studies for cannabidiol orodispersible tablets.

Obtaining orodispersible tablets (ODT) containing substances from the second Biopharmaceutical Class has raised concerns as the dissolution test is challenging. This study aimed to select suitable excipients for developing orodispersible tablets containing cannabidiol (CBD) by direct compression method. No similar studies were found in the literature. Excipients from different classes were characterized using the SeDeM-ODT tool: fillers - lactose (LCT) and microcrystalline cellulose (CelMC), sweeteners - sorbitol (SRB) and mannitol (MNT), disintegrants - sodium starch glycolate (SSG), sodium croscarmellose (CCS), soy polysaccharides (Emcosoy® - EMCS) and two co-processed excipients (Prosolv®-ODT G2 - PODTG2 and Prosolv® EasyTab sp - PETsp). Drug compatibility with excipients in binary mixtures (1:1) was verified by Differential Scanning Calorimetry (DSC) and Fourier Transform-Infrared (FTIR) spectroscopy. Using the SeDeM-ODT expert system, the fillers and the co-processed excipients showed good properties regarding compressibility and disintegration behavior. Also, the DSC and FTIR results showed that small or no interactions between the CBD and the excipients took place.

Impact of the Preparation Method on the Formulation Properties of Allantoin Hydrogels: Evaluation Using Semi-Solid Control Diagram (SSCD) Principles.

Allantoin possesses numerous beneficial properties for the skin, like anti-irritant effects, wound healing, skin hydration, and epithelization. In this paper, we investigated a suitable preparation method for an allantoin hydrogel using the Semi-Solid Control Diagram (SSCD) method and characterized its rheological and consistency behavior. To accomplish this, xanthan gum (XG) was selected as a model gelling agent. Briefly, four hydrogels were prepared, two without allantoin (coded M01 and M02) and two with allantoin (M1 and M2). Similarly, the formulations were either prepared through magnetic stirring (M01 and M1) or homogenization in a mortar (M02 and M2). The prepared hydrogels were evaluated using the SSCD for specific parameters and indexes. The Good Quality Index (GQI) shows a higher value for the formulation, M1 = 6.27, compared to M2 = 5.45. This result is also underlined by the value of M01 = 6.45, which is higher than M02 = 6.38. Considering the consistency, the formulation M01 possessed the highest spreadability, followed by M02 and then the allantoin hydrogels M1 and M2. The rheological behavior had a thixotropic pseudoplastic flow for all the formulations. The use of SSCD pictographs outlined the rheological properties that need improvement, the method that is suitable to prepare the allantoin hydrogels, and the influence of the allantoin suspended in the XG hydrogel.

Microencapsulation by Complex Coacervation of Lavender Oil Obtained by Steam Distillation at Semi-Industrial Scale.

Lavender oil (LEO) is one of the most well-known essential oils worldwide which, besides its extensive application in aromatherapy, serves as raw material for various fields, including the food, cosmetic, and pharmaceutical industries. Accordingly, several global requirements were established to warrant its quality. Microencapsulation represents an emerging technology widely applied for the preservation of essential oils, simultaneously providing new ways of application. In the current study, lavender oil was obtained from the flowering tops of Lavandula angustifolia Mill. on a semi-industrial-scale steam distillation system. According to the GC-MS investigation, lavender oil obtained in the third year of cultivation met the European Pharmacopoeia standards for linalyl acetate and linalool contents ≈38% and ≈26%, respectively. Microcapsules (MCs) containing the so-obtained essential oil were successfully produced by complex coacervation technology between gum arabic (GA) and three different grades of type-A gelatin (GE). Optical microscopic investigations revealed a significant difference in particle size depending on the gelatin grade used. The variation observed for coacervates was well reflected on the scanning electron micrographs of the freeze-dried form. The highest encapsulation efficiency values were obtained by UV-VIS spectrophotometry for microcapsules produced using gelatin with the medium gel strength. FT-IR spectra confirmed the structural modifications attributed to microencapsulation. According to the GC-MS analysis of the freeze-dried form, the characteristic components of lavender oil were present in the composition of the encapsulated essential oil.

Preparation and Evaluation of Caffeine Orodispersible Films: The Influence of Hydrotropic Substances and Film-Forming Agent Concentration on Film Properties.

This study aimed to develop caffeine (CAF) orodispersible films (ODFs) and verify the effects of different percentages of film-forming agent and hydrotropic substances (citric acid-CA or sodium benzoate-SB) on various film properties. Hydroxypropyl methylcellulose E 5 (HPMC E 5) orodispersible films were prepared using the solvent casting method. Four CAF-ODF formulations were prepared and coded as CAF1 (8% HPMC E 5, CAF), CAF2 (8% HPMC E 5 and CAF:CA-1:1), CAF3 (9% HPMC E 5 and CAF:CA-1:1), and CAF4 (9% HPMC E 5 and CAF:SB-1:1). The CAF-ODFs were evaluated in terms of disintegration time, folding endurance, thickness, uniformity of mass, CAF content, thickness-normalized tensile strength, adhesiveness, dissolution, and pH. Thin, opaque, and slightly white CAF-ODFs were obtained. All the formulations developed exhibited disintegration times less than 3 min. The dissolution test revealed that CAF1, CAF2, and CAF3 exhibited concentrations of active pharmaceutical ingredients (APIs) released at 30 min that were close to 100%, whilst CAF4 showed a faster dissolution behaviour (100% of the CAF was released at 5 min). Thin polymeric films containing 10 mg of CAF/surface area (3.14 cm2) were prepared.

The Influence of the Intergranular Superdisintegrant Performance on New Drotaverine Orodispersible Tablet Formulations.

The main objective of this study consists in establishing the influence of the intergranular superdisintegrant on the specific properties of drotaverine hydrochloride fast-dissolving granules (DROT-FDGs) and orodispersible tablets (DROT-ODTs). The orodispersible tablets were obtained by the compression of the FDGs and excipient mixture with an eccentric tableting machine. To develop DROT-ODTs, two types of superdisintegrant excipients in different concentrations (water-soluble soy polysaccharides (SSP) (1%, 5%) and water-insoluble soy polysaccharides-Emcosoy® STS IP (EMCS) (1%, 3%, 5%)) were used, resulting in five formulations (D1-D5). The DROT-FDGs and the DROT-ODTs were subjected to pharmacotechnical and analytical evaluation. All the orodispersible tablets obtained respect the quality requirements in terms of friability (less than 1%), crushing strength (ranging between 52 N for D2 and 125.5 N for D3), and disintegration time (<180 s). The in vitro release of drotaverine from ODTs showed that all formulations presented amounts of active substance released greater than 85% at 10 min. The main objective, developing 30 mg DROT-ODTs for children aged between 6 and 12 years by incorporating the API in FDGs, was successfully achieved.

Structural Characterization and Optimization of a Miconazole Oral Gel.

The development of semisolid formulations, gels in particular, has raised the attention of scientists more and more over the last decades. Because of their biocompatibility, hydrophilic nature, and capacity of absorbing large quantities of water, hydrogels are still one of the most promising pharmaceutical formulations in the pharmaceutical industry. The purpose of this study is to develop an optimal formulation capable of incorporating a water-poorly soluble active ingredient such as miconazole used in the treatment of fungal infections with Candida albicans and Candida parapsilosis. A D-optimal design was applied to study the relationship between the formulation parameter and the gel characteristics. The independent parameters used in this study were the Carbopol 940 concentration (the polymer used to obtain the gel matrix), the sodium hydroxide amount, and the presence/absence of miconazole. Ten different dependent parameters (Y1-Y10) were evaluated (penetrometry, spreadability, viscosity, and tangential tension at 1 and 11 levels of speed whilst destructuring and during the reorganization of the gel matrix). The consistency of the gels ranged from 23.2 mm (GO2) to 29.6 mm (GM5). The least spreadable gel was GO7 (1384 mm2), whilst the gel that presented the best spreadability was GO1 (3525 mm2). The viscosity and the tangential stress at the selected levels (1 and 11) varied due to the different compositions of the proposed gels. The gels were also tested for drug content and antifungal activity. All determinations had satisfying results; the drug content was within limits accepted by Ph. Eur. 10 and all formulations containing miconazole exhibited antifungal activity. An optimal formulation with miconazole was attained, consisting of 0.84% Carbopol 940 and 0.32% sodium hydroxide.

Development and Evaluation of Cannabidiol Orodispersible Tablets Using a 23-Factorial Design.

Orodispersible tablets (ODTs) are pharmaceutical formulations used to obtain fast therapeutic effects, usually recommended for geriatric and pediatric patients due to their improved compliance, bioavailability, ease of administration, and good palatability. This study aimed to develop ODTs with cannabidiol (CBD) phytocannabinoid extracted from Cannabis sativa used in the treatment of Lennox-Gastaut and Dravet syndromes. The tablets were obtained using an eccentric tableting machine and 9 mm punches. To develop CBD ODTs, the following parameters were varied: the Poloxamer 407 concentration (0 and 10%), the type of co-processed excipient (Prosolv® ODT G2-PODTG2 and Prosolv® EasyTab sp-PETsp), and the type of superdisintegrant (Croscarmellose-CCS, and Soy Polysaccharides-Emcosoy®-EMCS), resulting in eleven formulations (O1-O11). The following dependent parameters were evaluated: friability, disintegration time, crushing strength, and the CBD dissolution at 1, 3, 5, 10, 15, and 30 min. The dependent parameters were verified according to European Pharmacopoeia (Ph. Eur.) requirements. All the tablets obtained were in accordance with quality requirements in terms of friability (less than 1%), and disintegration time (less than 180 s). The crushing strength was between 19 N and 80 N. Regarding the dissolution test, only four formulations exhibited an amount of CBD released higher than 80% at 30 min. Taking into consideration the results obtained and using the Modde 13.1 software, an optimal formulation was developed (O12), which respected the quality criteria chosen (friability 0.23%, crushing strength of 37 N, a disintegration time of 27 s, and the target amount of CBD released in 30 min of 99.3 ± 6%).

Application of SeDeM expert systems in preformulation studies of pediatric ibuprofen ODT tablets.

Pediatric, ibuprofen containing orodispersible tablets (ODTs) were prepared using the SeDeM expert system methodology. In order to facilitate formulation, directly compressible ibuprofen was employed (Ibuprofen DC 8TM) and characterized using its SeDeM profile. The mannitol based superdisintegrant Ludiflash® was characterized by the SeDeM-ODT expert system, which also allowed calculation of the optimal excipient concentration in order to obtain suitable tablet hardness and disintegration time. After adding a sweetener and a standard combination of lubricants, the optimized formulation was directly compressed into tablets and evaluated in terms of tablet hardness, friability, disintegration time and dissolution profile. The SeDeM method was applied to determine the amount of corrective excipient (Ludiflash®) required for the compression of Ibuprofen DC 85TM in order to achieve suitable ODTs. Adequate tablet hardness, disintegration time, friability and dissolution profiles were found during tablet evaluation.