Propranolol HCL-loaded liposomes for intranasal delivery: in vitro and ex vivo evaluation of optimized formulation using design of experiments.

Aim: To develop a propranolol HCL-loaded liposomal nasal formulation for migraine prophylaxis. Materials & methods: Formulated the liposomes through thin layer hydration method and optimized via design of experiments (DOE). The prepared liposomes were characterized for particle size, zeta potential, PDI, drug entrapment and drug loading. Assessed for in vitro release kinetics, ex vivo permeability, histopathology and stability. Results: Optimized liposomes: 135.52 ± 5.87 nm, -19.9 ± 0.075 mV, 95.41 ± 0.05% entrapment, 43.37 ± 0.02% loading. Showed immediate (30.07 ± 2.09%) and sustained release (95.69 ± 4.58%) over 10 h. Enhanced permeation compared with controls; well-tolerated histopathologically. Conclusion: Liposomal formulation offers promise for intranasal propranolol HCL delivery in migraine prophylaxis, with stability under refrigeration.

Migraines (a type of long-lasting headache) can be helped by a medicine called propranolol HCL. In this study, scientists developed tiny bubbles, called liposomes, which contained propranolol HCL. The liposomes are designed to be inhaled via the nose, where the medicine is released slowly from the liposomes to treat the migraine. In this study, the researchers made the propranolol HCL-containing liposomes and analyzed them in the lab. They found that the liposomes were safe, and can be kept in a cool place for a long time. So, may be able to help treat migraines.

Sustainable Release of Propranolol Hydrochloride Laden with Biconjugated-Ufasomes Chitosan Hydrogel Attenuates Cisplatin-Induced Sciatic Nerve Damage in In Vitro/In Vivo Evaluation.

Peripheral nerve injuries significantly impact patients' quality of life and poor functional recovery. Chitosan-ufasomes (CTS-UFAs) exhibit biomimetic features, making them a viable choice for developing novel transdermal delivery for neural repair. This study aimed to investigate the role of CTS-UFAs loaded with the propranolol HCl (PRO) as a model drug in enhancing sciatica in cisplatin-induced sciatic nerve damage in rats. Hence, PRO-UFAs were primed, embedding either span 20 or 60 together with oleic acid and cholesterol using a thin-film hydration process based on full factorial design (24). The influence of formulation factors on UFAs' physicochemical characteristics and the optimum formulation selection were investigated using Design-Expert® software. Based on the optimal UFA formulation, PRO-CTS-UFAs were constructed and characterized using transmission electron microscopy, stability studies, and ex vivo permeation. In vivo trials on rats with a sciatic nerve injury tested the efficacy of PRO-CTS-UFA and PRO-UFA transdermal hydrogels, PRO solution, compared to normal rats. Additionally, oxidative stress and specific apoptotic biomarkers were assessed, supported by a sciatic nerve histopathological study. PRO-UFAs and PRO-CTS-UFAs disclosed entrapment efficiency of 82.72 ± 2.33% and 85.32 ± 2.65%, a particle size of 317.22 ± 6.43 and 336.12 ± 4.9 nm, ζ potential of -62.06 ± 0.07 and 65.24 ± 0.10 mV, and accumulatively released 70.95 ± 8.14% and 64.03 ± 1.9% PRO within 6 h, respectively. Moreover, PRO-CTS-UFAs significantly restored sciatic nerve structure, inhibited the cisplatin-dependent increase in peripheral myelin 22 gene expression and MDA levels, and further re-established sciatic nerve GSH and CAT content. Furthermore, they elicited MBP re-expression, BCL-2 mild expression, and inhibited TNF-α expression. Briefly, our findings proposed that CTS-UFAs are promising to enhance PRO transdermal delivery to manage sciatic nerve damage.

3D Printing of Mini Tablets for Pediatric Use.

In the treatment of pediatric diseases, suitable dosages and dosage forms are often not available for an adequate therapy. The use of innovative additive manufacturing techniques offers the possibility of producing pediatric dosage forms. In this study, the production of mini tablets using fused deposition modeling (FDM)-based 3D printing was investigated. Two pediatric drugs, caffeine and propranolol hydrochloride, were successfully processed into filaments using hyprolose and hypromellose as polymers. Subsequently, mini tablets with diameters between 1.5 and 4.0 mm were printed and characterized using optical and thermal analysis methods. By varying the number of mini tablets applied and by varying the diameter, we were able to achieve different release behaviors. This work highlights the potential value of FDM 3D printing for the on-demand production of patient individualized, small-scale batches of pediatric dosage forms.

Development of Lecithin/Chitosan Nanoparticles for Promoting Topical Delivery of Propranolol Hydrochloride: Design, Optimization and In-Vivo Evaluation.

Propranolol (PPL) administered orally is considered as the first line drug for the treatment of infantile hemangioma, however several systemic adverse effects limit its use. For this reason, our work tackles the development and evaluation of PPL loaded chitosan nanoparticles (NPs), as an effective alternative for the treatment of infantile hemangioma. PPL -NPs were prepared using the double emulsion technique and the influence of the formulation variables on drug entrapment efficiency (EE), particle size (PS), percent released after 24 h (%R24h) and zeta potential (ZP) were optimized using full factorial design. Two systems, namely F3 and F28 showing highest E.E., ZP and %R24h with lowest PS, were fully characterized for DSC and TEM and incorporated into hydrogel with adequate viscosity. After ensuring safety for the selected nanoparticle, the hydrogel containing the optimized system was applied topically to rats. The in-vivo skin deposition in rats showed an accumulation of propranolol from the lecithin/chitosan nanocarrier by 1.56-1.91-fold when compared to the drug solution. The obtained result was further supported by the confocal laser scanning microscopy which showed fluorescence across the skin. PPL-HCL-loaded lecithin/chitosan nanoparticles could be considered as a potential candidate for treating infantile hemangiomas (IH) by maintaining therapeutic concentration topically while minimizing systemic side effects.

Propranolol Hydrochloride Buccoadhesive Tablet: Development and In-vitro Evaluation.

Propranolol HCl is a beta blocker commonly used worldwide; however, it shows a low bioavailability due to its extensive first-pass metabolism. To overcome this problem, a novel drug delivery system such as buccoadhesive system might be helpful. The aim of the present investigation is to prepare the buccoadhesive tablet of propranolol HCl using different mucoadhesive polymers. Buccoadhesive tablets containing drug, lactose, and polymers such as HPMC K4M, carbomer 934P, PEO 8000000 and PEG 6000, in various concentrations, were prepared. The tablets were evaluated in terms of weight variation, thickness, hardness, friability, and mucoadhesive strength. Among thirteen prepared formulations, seven of them which had better physicochemical properties and mucoadhesive strength were undergone the release and swelling tests. Finally, two formulations were selected and uniformity, drug content, duration of mucoadhesion, and kinetic studies were performed for them. All polymers except PEG 6000 were appropriate for being used in buccal mucoadhesive systems. Formulation F1 was considered as the most desirable formulation as it exhibited appropriate mucoadhesive strength (43.93 ± 12.4 g), extended duration of mucoadhesion (19.15 ± 0.29 h) and suitable swelling ability while having a prolonged drug release over 12 h. Although the efficiency and mucosal irritation of propranolol HCl buccoadhesive tablets should be monitored under the in-vivo conditions, however, based on the results, it seems that such tablets can be considered as an alternative route to bypass the first pass metabolism of propranolol HCl.

Logic of Selecting Suitable Dissolution Parameters in New Drug Formulations Based on A BCS Approach.

Since the biopharmaceutical quality of generic drug formulations depends on the quality of the reference products and also information about the in-vitro release performance of drugs under different conditions is scarce in the literature, a dissolution study of four reference tablets was performed. Each drug was representative of one Class of the Biopharmaceutical Classification System. The in-vitro release performance of propranolol-HCl, carbamazepine, ranitidine-HCl, and metronidazole was evaluated using a USP basket and paddle apparatus at different agitation rates (50, 75, and 100 rpm) with two doses of each drug. In all experiments, pharmacopeial dissolution media was used and the samples were taken with automatic equipment at specific times up to 60 min, except for propranolol-HCl, for which the samples were taken up to 30 min. The dissolution profiles were compared by model-independent, model-dependent, and ANOVA-based comparisons. The three methods of data comparison showed that low vs. high doses were significantly different (P < 0.05), which may influence cases in which biowaivers of propranolol-HCl and ranitidine-HCl are requested. Additionally, the results showed that despite different hydrodynamic environments produced by the basket and paddle apparatus, under certain conditions, both types of equipment generated comparable in-vitro results. Variables such as the dose, agitation rate, and type of dissolution apparatus are important factors to consider in designing dissolution tests for drug products. This information can be used to test a new dosage when there is no pharmacopeial method available to perform a dissolution study. Further researches on the in-vitro release performance of reference drug products are required.

Development of a 3D Printed Coating Shell to Control the Drug Release of Encapsulated Immediate-Release Tablets.

The use of 3D printing techniques to control drug release has flourished in the past decade, although there is no generic solution that can be applied to the full range of drugs or solid dosage forms. The present study provides a new concept, using the 3D printing technique to print a coating system in the form of shells with various designs to control/modify drug release in immediate-release tablets. A coating system of cellulose acetate in the form of an encapsulating shell was printed through extrusion-based 3D printing technology, where an immediate-release propranolol HCl tablet was placed inside to achieve a sustained drug release profile. The current work investigated the influence of shell composition by using different excipients and also by exploring the impact of shell size on the drug release from the encapsulated tablet. Three-dimensional printed shells with different ratios of rate-controlling polymer (cellulose acetate) and pore-forming agent (D-mannitol) showed the ability to control the amount and the rate of propranolol HCl release from the encapsulated tablet model. The shell-print approach also showed that space/gap available for drug dissolution between the shell wall and the enclosed tablet significantly influenced the release of propranolol HCl. The modified release profile of propranolol HCl achieved through enclosing the tablet in a 3D printed controlled-release shell followed Korsmeyer-Peppas kinetics with non-Fickian diffusion. This approach could be utilized to tailor the release profile of a Biopharmaceutics Classification System (BCS) class I drug tablet (characterized by high solubility and high permeability) to improve patient compliance and promote personalized medicine.

Acrylamide grafted neem (Azadirachta indica) gum polymer: Screening and exploration as a drug release retardant for tablet formulation.

The study was initiated with the intent to synthesize acrylamide grafted neem gum polymer (AAm-g-NG), and screen its drug release retardation ability both in vitro and in vivo. Different batches (NGP-1 to NGP-9) of tablet formulation were prepared by varying polymer concentration using propranolol HCl and compared with HPMC K100 M and marketed SR tablets. FTIR study proved the grafting phenomenon and showed no incompatibility between AAm-g-NG and propranolol HCl. AAm-g-NG showed significant swelling and water retention capacity than NG. AAm-g-NG was found to be biodegradable and exhibited no toxicity to Artemia salina. After 12 h, NGP-6 showed non-significant (p > 0.05; f2= ∼ 90) percent drug release (80.52 ±â€¯3.41%) compare to marketed formulation (79.65 ±â€¯4.08%). Significant swelling of the matrix caused slower diffusion of the drug. NGP-6 and marketed formulation in rabbits showed the non-significant difference between Cmax and Tmax, hence NGP-6 meets the requirement of sustained-release tablets.

Radiation preparation of L-arginine/acrylic acid hydrogel matrix patch for transdermal delivery of propranolol HCl in hypertensive rats.

In the present study, L-arginine/acrylic acid (Arg/AAc) batch hydrogel was successfully prepared by gamma irradiation for transdermal delivery of propranolol HCl in hypertensive rats. The resulted system has been characterized by FTIR to confirm the hydrogel formation. The swelling behavior of the prepared hydrogels was investigated as a function of time and pH. The kinetics of swelling has been investigated. In vivo pharmacokinetics evaluation, skin irritation test, and histopathological studies were investigated. Furthermore, the antihypertensive efficacy of transdermal propranolol-loaded Arg/AAc hydrogel on methyl prednisolone acetate-induced hypertensive rats was evaluated. It was found that the prepared patches exhibited a sustained release of the drug into systemic circulation over oral route which is subjected to hepatic first-pass metabolism, coupled with a short plasma half-life. Transdermal administration displayed a prolonged antihypertensive effect in spontaneously hypertensive rats. Moreover, the skin irritation test and histopathological examination indicated that the prepared patches are not irritant and can be safely applied on the skin. These results indicated that the hydrogel system composed of Arg and AAc has potential as a transdermal delivery system.

Buccal administration of mucoadhesive blend films saturated with propranolol loaded nanoparticles.

The aims of this study were to prepare and characterize hydroxypropyl methylcellulose (HPMC)/polycarbophil (PC) mucoadhesive blend films saturated with propranolol hydrochloride (PNL)-loaded nanoparticles to improve permeability of drugs that undergo first-pass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL (70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles (PN-films) and HPMC/PC blend films containing PNL (80 mg/film) without nanoparticles (PP-films) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope (SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film (PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index (SI) of all PN-films and PP-films increased greatly in the first period time (10-20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points (10-30 min). After 120 min, the release of PN-films-70 was lower than the other PN-films. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.

Transdermal delivery of propranolol hydrochloride through chitosan nanoparticles dispersed in mucoadhesive gel.

This study aimed at improving the systemic bioavailability of propranolol-HCl by the design of transdermal drug delivery system based on chitosan nanoparticles dispersed into gels. Chitosan nanoparticles were prepared by ionic gelation technique using tripolyphosphate (TPP) as a cross-linking agent. Characterization of the nanoparticles was focused on particle size, zeta potential, surface texture and morphology, and drug encapsulation efficiency. The prepared freeze dried chitosan nanoparticles were dispersed into gels made of poloxamer and carbopol and the rheological behaviour and the adhesiveness of the gels were investigated. The results showed that smallest propranolol loaded chitosan nanoparticles were achieved with 0.2% chitosan and 0.05% TPP. Nanoparticles were stable in suspension with a zeta potential (ZP) above ±30mV to prevent aggregation of the colloid. Zeta potential was found to increase with increasing chitosan concentration due to its cationic nature. At least 70% of entrapment efficiency and drug loading were achieved for all prepared nanoparticles. When chitosan nanoparticles dispersed into gel consisting of poloxamer and carbopol, the resultant formulation exhibited thixotropic behaviour with a prolonged drug release properties as shown by the permeation studies through pig ear skin. Our study demonstrated that the designed nanoparticles-gel transdermal delivery system has a potential to improve the systemic bioavailability and the therapeutic efficacy of propranolol-HCl.

Comparative evaluation of drug release from aged prolonged polyethylene oxide tablet matrices: effect of excipient and drug type.

Polyethylene oxide (PEO) undergoes structural adjustments caused by elevated temperatures, which results in loss of its stability within direct compression tablets. The aim of this study was to evaluate the influence of filler solubility on the drug delivery process of matrix tablets containing drugs with different water-solubility properties and stored at elevated temperature. The results demonstrated that in the case of propranolol HCl (highly water-soluble) tablet matrices, soluble lactose promoted drug release, whereas, a stable release of drug was observed with insoluble DCP. A drug release pattern similar to the propranolol HCl formulation containing DCP was obtained for hydrophilic matrix tablets containing either lactose or DCP for the less water-soluble drug, zonisamide. In the case of the partially water-soluble drug, theophylline, formulated with lower molecular weight PEO 750, drug release increased considerably in the presence of both fillers with increasing storage time, however a stable release rate (similar to fresh samples) was observed in the case of higher molecular weight PEO 303 tablet matrices containing theophylline with either lactose or DCP. The hydration properties (e.g. solubility) of the diluents had a considerable effect on drug release behavior from various model matrices; this effect was dependent on both molecular weight of PEO and solubility of drug.

Chronotherapeutic drug delivery of Tamarind gum, Chitosan and Okra gum controlled release colon targeted directly compressed Propranolol HCl matrix tablets and in-vitro evaluation.

The main objective of this investigation is to develop a chronotherapeutic drug delivery of various natural polymers based colon targeted drug delivery systems to treat early morning sign in BP. The polymers such as Tamarind gum, Okra gum and Chitosan were used in the formulation design. A model drug Propranolol HCl was incorporated in the formulation in order to assess the controlled release and time dependent release potential of various natural polymers. A novel polymer Tamarind gum was extracted and used as a prime polymer in this study to prove the superiority of this polymer over other leading natural polymer. Propranolol HCl was used as a model drug which undergoes hepatic metabolism and witnesses the poor bioavailability. The matrix tablets of Propranolol HCl were prepared by direct compression. The tablets were evaluated for various quality control parameters and found to be within the limits. Carbopol 940 was used as an auxiliary polymer to modify the drug release and physicochemical characteristics of the tablets. The in vitro release studies were performed in 0.1N HCl for 1.5h, followed by pH 6.8 phosphate buffer for 2h and pH 7.4 phosphate buffer till maximum amount of drug release. The in vitro release profile of the formulations were fitted with various pharmacokinetic mathematical models and analyzed for release profile. The formulations prepared with Tamarind gum prolonged the release for an extended period of time compared to other polymer based formulation and showed an excellent compression characteristic.

Epinephrine as adjuvant for propranolol produces a marked peripheral action in intensifying and prolonging analgesia in response to local dorsal cutaneous noxious pinprick in rats.

The aim of this study was to evaluate the effect of epinephrine as additive for propranolol as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we tested the effect of co-administration of epinephrine with propranolol on infiltrative cutaneous analgesia. Bupivacaine, a long-lasting local anesthetic, was used as control. Subcutaneous propranolol and bupivacaine elicited a dose-dependent local anesthetic effect on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the relative potency was bupivacaine [2.05 (1.95-2.21) µmol/kg]>propranolol [9.21 (9.08-9.42) µmol/kg] (P<0.01 for each comparison). Subcutaneous epinephrine (0.012 µmol/kg) did not produce cutaneous analgesia. Mixtures of epinephrine (0.012 µmol/kg) with drugs (propranolol or bupivacaine) at ED50 or ED95, respectively, intensified and prolonged drug action on infiltrative cutaneous analgesia. Intraperitoneal injection of combined drugs (propranolol or bupivacaine) at ED95 with epinephrine (0.012 µmol/kg) exhibited no cutaneous analgesia. We concluded that propranolol was less potent but produced a similar duration of action when compared to bupivacaine on infiltrative cutaneous analgesia. Epinephrine as adjuvant for propranolol or bupivacaine enhanced the potency and extended the duration of action on infiltrative cutaneous analgesia.

Formulation of gastroretentive floating drug delivery system using hydrophilic polymers and its in vitro characterization

The aim of the present research is to formulate and evaluate the gastroretentive floating drug delivery system of antihypertensive drug, propranolol HCl. Gastroretentive floating tablets (GRFT) were prepared by using a synthetic hydrophilic polymer polyethylene oxide of different grades such as PEO WSR N-12 K and PEO 18 NF as release retarding polymers and calcium carbonate as gas generating agent. The GRFT were compressed by direct compression strategy and the tablets were evaluated for physico-chemical properties, in vitro buoyancy, swelling studies, in vitro dissolution studies and release mechanism studies. From the dissolution and buoyancy studies, F 9 was selected as an optimized formulation. The optimized formulation followed zero order rate kinetics with non-Fickian diffusion mechanism. The optimized formulation was characterised with FTIR studies and observed no interaction between the drug and the polymers.

O objetivo da presente pesquisa é o de formular e avaliar o sistema de liberação de fármaco gastrorretentivo flutuante, contendo o anti-hipertensivo, cloridrato de propranolol. Comprimidos gastrorretentivo flutuantes (GRFT) foram preparados utilizando um polímero hidrofílico sintético, o óxido de polietileno, de diferentes graus, tais como GE WSR N-12 K e GE 18 NF, como polímeros de retardamento de liberação, e carbonato de cálcio, como agente gerador de gases. Os GRFT foram comprimidos por compressão direta e avaliados para determinação das propriedades físico-químicas, flutuabilidade in vitro, estudos de inchamento, de dissolução in vitro e de mecanismo de liberação. Dos testes de dissolução e de flutuabilidade, selecionou-se F 9 como formulação otimizada. A formulação otimizada seguiu cinética de ordem zero, com mecanismo de difusão não-Fickiano. Essa formulação foi caracterizada por estudos de FTIR, não se observando interação entre o fármaco e os polímeros.

Thermal sintering: a novel technique in the design of gastroretentive floating tablets of propranolol HCl and its evaluation / Sinterización térmica: Una técnica novedosa en el diseño de tabletas flotantes gastroretentivas de HCl propanolol y su evaluación

The aim of the present investigation was to formulate thermally sintered floating tablets of propranolol HCl, and to study the effect of sintering conditions on drug release, as well as their in vitro buoyancy properties. A hydrophilic polymer, polyethylene oxide, was selected as a sintered polymer to retard the drug release. The formulations were prepared by a direct compression method and were evaluated by in vitro dissolution studies. The results showed that sintering temperature and time of exposure greatly influenced the buoyancy, as well as the dissolution properties. As the sintering temperature and time of exposure increased, floating lag time was found to be decreased, total floating time was increased and drug release was retarded. An optimized sintered formulation (sintering temperature 50°C and time of exposure 4 h) was selected, based on their drug retarding properties. The optimized formulation was characterized with FTIR and DSC studies and no interaction was found between the drug and the polymer used.

El propósito de la presente investigación fue la elaboración de tabletas flotantes de HCL propanolol térmicamente sinterizadas y estudiar los efectos de las condiciones de sinterización sobre la liberación de la droga, así como sobre sus propiedades de flotabilidad in vitro. Se seleccionó un polímero hidrofílico, el óxido de polietileno, como polímero sinterizado, para retardar la liberación de la droga. Las fórmulas se prepararon mediante un método de compresión directa y se evaluaron mediante estudios de disolución in vitro. Los resultados demostraron que la temperatura de sinterización y el tiempo de exposición tuvieron una gran influencia sobre las propiedades de flotabilidad y de disolución. Se encontró que el intervalo de retardo en la flotación disminuyó, el tiempo total de flotación aumentó y se retardó la liberación de la droga, a medida que aumentaron la temperatura de sinterización y el tiempo de exposición. Se seleccionó una fórmula óptima de sinterización (temperatura de sinterización de 50°C y tiempo de exposición de 4 h), basados en las propiedades retardativas sobre la droga. La fórmula sinterizada se caracterizó mediante estudios FITR y DSC y no se encontró ninguna interacción entre la droga y el polímero utilizado.

Design and in vitro evaluation of effervescent gastric floating drug delivery systems of propanolol HCl / Diseño y evaluación in vitro de sistemas de administración de tabletas flotantes gástricas everfescentes de HCl propanolol

The purpose of this research was to develop and evaluate effervescent gastric floating tablets of propranolol HCl. The oral delivery of antihypertensive propranolol HCl was facilitated by preparing an effervescent floating dosage form which could increase its absorption in the stomach by increasing the drug’s gastric residence time. In the present work, effervescent floating tablets were prepared with a hydrophilic carrier such as polyethylene oxide (PEO WSR N 60K and PEO WSR 303) as a release retarding agent and sodium bicarbonate as a gas generating agent. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, drug release and rate order kinetics. From the results, P9 was selected as an optimized formulation based on their 12 h drug release, minimal floating lag time and maximum total floating time. The optimized formulation followed first order rate kinetics with erosion mechanism. The optimized formulation was characterized with FTIR studies and no interaction between the drug and the polymers were observed.

El propósito de la presente investigación fue desarrollar y evaluar tabletas flotantes, efervescentes de HCL propranolol. La administración oral del antihipertensivo HCL propranolol se facilitó mediante la preparación de una forma de dosificación flotante y efervescente que permitiría su absorción en el estómago, mediante el aumento del tiempo de residencia gástrico de la droga. En el presente trabajo, las tabletas flotantes efervescentes fueron preparadas con un portador hidrofílico, tal como el óxido de polietileno (PEO WSR N 60K and PEO WSR 303), como agente retardador y bicarbonato de sodio como un agente generador de gas. Se evaluaron todas las propiedades fisicoquímicas de las tabletas preparadas, su flotación in vitro y su tasa de orden cinético. Se seleccionó el P9 a partir de los resultados obtenidos, como una fórmula óptima, basados en la liberación de la droga a las 12 h, tiempo mínimo de retraso para flotación y máximo tiempo total de flotación. La formulación optimizada siguió una tasa cinética de primer orden con mecanismo de erosión. Esta fórmula óptima se caracterizó mediante estudios FITR y no se observó ninguna interacción entre la droga y los polímeros utilizados.

Development and In-vitro Evaluation of a Contraceptive Vagino-Adhesive Propranolol Hydrochloride Gel.

The objective of the present investigation was to develop and evaluate a contraceptive vagino-adhesive propranolol hydrochloride gel. To achieve this, various mucoadhesive polymers including guar gum (1-4% w/w), sodium alginate (4-7% w/w), xanthan gum (2-5% w/w ), HPMC 4000 (3-5% w/w), Na CMC (4-7% w/w), carbomer 934 and carbomer 940 both in the range of 0.5-2.0% w/w, were dispersed in an aqueous-based solution containing the drug (1.6% w/w). The mucoadhesive properties of the gels were assessed on sheep vaginal mucosa (as model mucosa) in pH 4.5 citrate-phosphate buffer at 37°C. Formulations containing charged functional groups in their polymeric structure, showed higher mucoadhesive strengths in comparison to those composed of neutral polymers. In-vitro drug release profiles of the gels were determined in pH 4.5 citrate-phosphate buffer. Results indicated that, only formulation F13 (containing sodium alginate 6.5% w/w), could release its drug over 12 h, with a burst release at the initial phase followed by a sustained release pattern. This formulation, which showed a good mucoadhesive strength (386.97 ± 9.31 mN), was considered as the final formulation and underwent complementary tests including determination of drug content and duration of mucoadhesion. Its drug content was found to be 101.05 ± 0.106% (n = 3) and it attached to the model mucosa for more than 10 h. In conclusion, formulation F13 was considered as the most desirable formulation as it exhibited appropriate mucoadhesive properties while having the potential of providing an immediate contraceptive effect, followed by a prolonged drug release which is assumed to render longer contraceptive efficacy.

Determination of the binding sites of propranolol HCl on bovine serum albumin by direct and reverse procedures.

To characterize the binding site of propranolol hydrochloride, the free concentration of warfarin (site-I-specific probe) bound to BSA was measured upon the addition of propranolol hydrochloride. It was found that the free concentration of warfarin sodium was increased from 100% (as % of initial) to 552.35% when the ratio of propranolol to BSA was increased 1-6. In contrast, under the same experimental conditions, when diazepam was used as a site-II-specific probe, the increment of the free concentration of diazepam by propranolol was from 100% (as % of initial) to 415.42. From these data it is evident that the increment of free concentration of warfarin sodium is obviously greater than that of diazepam by propranolol. So it can be concluded that propranolol preferentially binds to site-I. Again as the displacement of diazepam is quite enough it can also be suggested that propranolol in addition to site-I also binds to site-II on the BSA molecule but to a lower extent. Again in the reverse experiment, the free concentration of propranolol was increased from 100% (as % of initial) to 476% when warfarin to BSA ratio was 1-6 as shown, on the other hand, the free concentration of propranolol was increased from 100% (as % initial) to 222.39% when the ratio of diazepam to BSA was also 1-6. From the data it is clear that the increment of propranolol due to displacement by warfarin (site-I probe) is higher than that of propranolol when displaced by diazepam (site-II probe). Thus this reverse experiment also agrees with the previous experiment.