Immunomodulatory effect of Unani polyherbal formulation - Tiryaq Wabai in mild to moderate COVID-19 patients - A randomized placebo-controlled clinical trial.

BACKGROUND: The pathogenesis of COVID-19 includes an integrated immune-inflammatory response. Modulation of host immune responses against the SARS-CoV-2 virus might be effective therapeutic management. Various Unani formulations have an immunomodulatory effect. OBJECTIVE: To explore the immunomodulatory effect and safety of Unani polyherbal drug (Tiryaq Wabai) in COVID-19 patients. MATERIALS AND METHODS: The current study was a randomized placebo-controlled clinical trial that included 92 mild to moderate COVID-19 patients randomized into two groups. The Unani formulation Tiryaq Wabai (2 gm orally once a day) was used as an intervention for 45 days, while the control group received a placebo. Both groups received standard care treatment. The primary outcome was 50% increment in absolute lymphocyte count (ALC). The secondary outcome was 50% increment in mean lymphocyte percentage, CD4 cells, and CD8 cell count. The mean increase in all the above parameters has also been studied. Relevant statistical tests were used to analyze the effect. RESULTS: A statistically significant improvement in a 50% increase in ALC (p-value, 0.004), lymphocyte percentage (p-value, 0.056), CD4 (p-value, 0.005), and CD8 cell count (p-value, 0.050) was reported. Also, a significant improvement in the mean value of the lymphocyte percentage (p-value 0.0007), ALC (p-value 0.0022), CD4 cell count (p-value 0.0025), and CD8 cell count (p-value 0.0093) was observed after the treatment. One adverse event of mild grade was reported in the placebo group. The analysis of safety parameters (LFT and KFT) was normal for both groups. CONCLUSION: In mild to moderate COVID-19 patients, Tiryaq Wabai effectively showed immunomodulatory activity by improving ALC count, lymphocyte percentage, CD4, and CD8 cell count.

An Exploratory Review on the Hypoglycemic Action of Unani Anti-diabetic Drugs via Possible Modulation of Gut Microbiota.

BACKGROUND AND AIM: Diabetes mellitus is a chronic, multi-factorial metabolic disorder and also an important public health issue that requires multi-dimensional therapeutic strategies for effective control. Unani herbs have long been used to effectively mitigate diabetes through various mechanisms. In recent years, it has been speculated that the alteration of gut microbiome ecology is potentially one of the important mechanisms through which the Unani drugs exert hypoglycemic action. This review aims at the trans-disciplinary interpretation of the holistic concepts of the Unani system of medicine and the molecular insights of contemporary medicine for novel strategies for diabetes management. METHODOLOGY: We searched scientific databases such as PubMed, Google Scholar, and Science-Direct, etc. Unani classical texts (Urdu, Arabic, and Persian), and medical books, for diabetic control with Unani medicine through the gut microbiome. RESULTS: Unani medicine defines, diabetes as a urinary system disorder disrupting the transformational faculty (Quwwat Mughayyira) in the gastrointestinal tract. The Unani system and contemporary biomedicine use different epistemology and ontology for describing diabetes through gutderived factors in whole-body glucose homeostasis. Unani Pharmaceutics have reported in clinical and preclinical (in vitro/ in vivo) trials in improving diabetes by altering gut microbiota composition, microvascular dysfunction, and inflammation. However, the preventive plan is the preservance of six essential factors (Asbab Sitta Daruriyya) as a lifestyle plan. CONCLUSION: This is the first study on the integrative strategy about the hypoglycemic effects of Unani herbs that could serve as a prerogative novel approach for cost-effective, holistic, rationalistic, and multi-targeted diabetes management.

Interventions of Unani medicine for maintenance of health with special reference to air quality: an evidence-based review.

OBJECTIVES: This article aims to discuss the impact of air quality on human health, measures to achieve the goal of good indoor air quality and proposed benefits of interventions of Unani Medicine with an evidence-based approach. CONTENT: The significance of air quality on the health of the community cannot be denied. Recent evidences from WHO illustrated data on severe air pollutants and their impacts on human health ranges from minor upper respiratory irritation to chronic respiratory ailments including lung carcinoma and heart disease associated with premature mortality and reduced life expectancy. In Unani Medicine, air has been included in the list of factors, which are six in number and play the central role in prevention of diseases and maintenance of health. Air is considered as the medium of most of the extrinsic factors such as chemical and biological pollutants affecting health and their exposure results in short and long-term health issues. The literature of Unani Medicine proposes many simple and effective measures, which help to improve indoor and outdoor air quality. The goal of outdoor clean air is achieved through implementation of measures to tackle the source of pollution, while indoor clean air is attained through various means e.g., fumigation with herbal drugs. Hence, an extensive literature survey on Unani reserve was conducted to collect information about the concept of air discussed under the heading of six essential factors and its implication in prevention of diseases and maintenance of health. Further, research databases such as Pub Med, Google Scholar, and Science-Direct were broadly searched for evidence on the efficacy of herbals mentioned in Unani literature for the indoor air purification and subsequent air quality improvement. SUMMARY AND OUTLOOK: Recent studies showed good air quality leads to decrease in mortality, particularly of respiratory and cardiovascular deaths whereas poor air quality results in a variety of diseases. Unani scholars prescribed several regimens such as Bukhoor (Fumigation), Sa'oot (Nasal instillation) and use of Abeer (Perfumes) and Nadd (Incense) for the improvement of air quality. Likewise various herbal fumigants and sprays containing drugs like mi'a sa'ila (Liquidambar orientalis Mill.), mastagi (Pistacia lentiscus L.), mushk (Moschus moschiferus L.), loban (Styrax benzoides W. G. Craib), abnoos (Diospyros ebenum J. Koenig ex Retz), za'fran (Crocus sativus L.) and sirka (vinegar) etc. has been well explained and used exclusively for air purification and improvement of AQI. Therefore, in the present scenario of altered air quality, we forward certain measures described in Unani system of medicine for health promotion and protection. Scientific evidence on several drugs reveal the presence of a number of pharmacologically active substances, which may provide a new approach into the purification of air.

Concept of Unani Jali (detergents/cleansers) drugs and its scientific validation: scope for new opportunities in dermatological pharmacotherapeutics.

OBJECTIVES: The use of detergent-action drugs in traditional Unani therapeutic intervention has been a long-standing Unani medicinal practice. The key aim of the article is to provide thorough information on the novel, unexplored idea of Unani Jali (detergent/cleansers) drugs for the treatment of skin ailments, as well as to identify medicinal plants that have detergent action and correlate these findings with scientific studies that may support evidence for the drug's detergent effect. CONTENT: The ethnobotanical classical literature of Unani medicine was investigated in order to have a comprehensive insight of Unani detergents/cleansers. Scientific studies were carried from databases including PubMed, Scopus, Science Direct, and google Scholar, among others. More than fifty exclusive plant, mineral, and animal-based detergents are found specifically for skin disorders in Unani therapy. These drugs basically evacuate impurities from the body's excretory system and and have been found to have keratolytic and debris-peeling effects, as well as the ability to maintain skin tone consistency. Unani Jali drugs have also been found to have anti-inflammatory, antibacterial, analgesic, and tonic properties, suggesting its usefulness holistically. SUMMARY AND OUTLOOK: Based on phyto constituents, prospective therapeutic response, and scientific data, this review proposes that Unani Jali drugs could be a safe and promising therapeutic option for dermatological illnesses such as vitiligo, acne, dermatitis, psoriasis, and skin sensitivity.

Therapeutic and palliative role of a Unani herbal decoction in COVID-19 and similar respiratory viral illnesses: Phytochemical & pharmacological perspective.

ETHNOPHARMACOLOGICAL RELEVANCE: Outbreaks of respiratory viral infections like Severe Acute Respiratory Syndrome, Middle-East Respiratory Syndrome, and Coronavirus Disease-2019 have been a regular occurrence in the past 100 years. A significant proportion of the morbidity and mortality in influenza is attributed to the co-morbidities and complications induced by the disease, involving the vital organs and physiological functions. In this context, traditional medicines offer effective protective, palliative, and therapeutic benefits, as observed in several studies on various types of influenza, including COVID-19. The Unani herbal decoction comprising of 'Unnab (Ziziphus jujuba Mill. fruit), Sapistan (Cordia dichotoma G. Forst. fruit), and Behidana (Cydonia oblonga Mill. seed) was originally prescribed by Hakim Ajmal Khan (1868-1927 AD) for various respiratory ailments as a bronchodilator, anti-inflammatory, and for clearing the respiratory tract. During COVID-19, the decoction was prescribed by the Ministry of Ayurveda, Yoga, Unani, Siddha, and Homeopathy (AYUSH), Government of India, for mild patients in home isolation, and also as a self-care drink for healthy people. Preliminary studies are of the view that the decoction could reduce COVID-19 incidence and prevent severe disease in the population where it was administered. AIMS OF THE STUDY: We intend to review the pharmacological activity of the Unani decoction ingredients, i.e., Z. jujuba, C. dichotoma, and C. oblonga, in context with respiratory viral infections and their co-morbidities, to develop an understanding of its action mechanism. METHODOLOGY: We reviewed Unani classical textbooks for information on the therapeutic activity of the decoction ingredients. Scientific studies published in English from the year 2000 onwards on leading scientific websites (PubMed, MEDLINE, Scopus, and Springer) were searched for information regarding the efficacy of the drugs in influenza and its common complications. Non-English language articles, or those published prior to 2000, and those which included plant parts other than those traditionally included in the decoction were excluded. OBSERVATIONS: A wide range of therapeutic and palliative effects have been observed in the three herbs included in the Unani decoction, including anti-viral, anti-bacterial, immuno-modulatory, anti-inflammatory, hepato-, and nephroprotective, anti-atherosclerotic, anti-tussive, broncho-dilatory, and regulation of gut microbiota. Together, these effects can help to mitigate and prevent most of the complications caused as a result of respiratory viral infections. CONCLUSION: The combined effects of ingredients in this Unani herbal decoction can potentially help to mitigate most of the pathological changes and complications caused by influenza viruses. With further clinical research, the decoction may be potentially utilized as a prophylactic and therapeutic against viral influenza.

Why the "sugars" in traditional Unani formulations are a pivotal component: A viewpoint perspective.

Traditional medicine systems around the globe, like Unani, Ayurveda and traditional Chinese medicine, include a number of sugar-based formulations, which contain a large amount of saccharide-containing sweetener, such as honey, sucrose or jaggery. With pervasive lifestyle disorders throughout the world, there have been discussions to consider alternative sweetening agents. Here, from the perspective of Unani medicine, we discuss how the saccharide-based sweeteners may be an essential component of these traditional preparations, like electuaries, which may be deprived of their bioactivities without these saccharides. With contemporary researches, it is known that apart from their own therapeutic effects, saccharides also form deep eutectic solvents which help in enhancing the bioactivity of other ingredients present in crude drugs. In addition, they provide energy for fermentation which is essential for biotransformation of compounds. Interestingly, the sugars also increase the shelf-life of these compound drugs and act as natural preservatives. On the basis of this review, we strongly believe that saccharide-based sweeteners are an essential component of traditional medicines and not merely an excipient.

Role of herbal medicines in the management of patients with COVID-19: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: The management of the worldwide spreading COVID-19 consists of amelioration of its symptoms but no cure is yet available. Herbal medicines supplemented with the Western medicine have been applied for COVID-19 treatment in India, China, Iran, and other countries. This systematic review and meta-analysis of RCTs evaluates the effect and safety of herbal intervention in the management of COVID-19. EXPERIMENTAL PROCEDURE: RCTs from databases like PubMed, Cochrane Library, ScienceDirect, Google Scholar, Science Direct, CTRI, AYUSH Research Portal, India, were reviewed and the data were extracted for study sample demographics, intervention details, clinical effect, inflammatory markers and safety monitoring. Outcomes were expressed as Risk-ratio (RR) with 95% CI for dichotomous data, and Mean-Difference (MD) with 95% CI for continuous data. RESULT AND CONCLUSION: From the 32 eligible studies, a total of 3177 COVID-19 patients were included in the review. Herbal intervention as an adjuvant to Western medicine causes significantly higher improvement compared to Western medicine alone [Fever (RR = 1.09 CI 1.03, 1.15), Cough (Risk-Ratio = 1.22 CI 1.08, 1.37), Fatigue (Risk-Ratio = 1.27 CI 1.11, 1.44), Chest CT Improvement (Risk-Ratio = 1.15 CI 1.08, 1.23)]. The laboratory parameters were also better in the herbal medicine group compared to standard care group only WBC (MD = 0.36 CI 0.16, 0.55), Lymphocyte percentage (MD = 5.48 CI 3.05, 7.92), Absolute lymphocyte count (MD = 0.23 CI 0.07, 0.39), CRP (MD = -5.66 CI -7.96, -3.37). However, duration of hospital stays (MD = -1.82 CI -3.84, 0.21); IL-6 (MD = -3.67 CI -8.76, 1.43), ESR Level (MD = -10.38 CI -25.96, 5.21) were statistically insignificant. No significant adverse events for herbal medications were noted in the included RCTs, during the time of the studies. (n = 665, RR 0.93; 95% CI 0.76, 1.14).

History, phytochemistry, experimental pharmacology and clinical uses of honey: A comprehensive review with special reference to Unani medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Honey is one of the most popular functional foods, speculated to be in use since the advent of human civilization. Its health-protective activity is endorsed by many religions and traditional medicines. In Unani medicine, honey is prescribed for many health conditions as wound-healing, anti-inflammatory, anti-diabetic, etc. In the present era, honey is gaining popularity over sugar for its myriad health benefits and low glycemic index. This review attempts to provide a comprehensive account of the biological activities and potential therapeutic uses of honey, with scientific evidence. METHODOLOGY: In this paper, we have provided a comprehensive overview of historical uses, types, physical characteristics, bioactive constituents and pharmacological activities of honey. The information was gathered from Classical Unani textbooks and leading scientific databases. There is a plethora of information regarding various therapeutic activities of honey, and it is daunting to draw practical conclusions. Hence, in this paper, we have tried to summarize those aspects which are most relevant to clinical application. OBSERVATIONS AND CONCLUSIONS: Many important bioactive constituents are identified in different honey types, e.g. phenolics, proteins, vitamins, carbohydrates, organic acids, etc., which exert important biological activities like anti-microbial, wound healing, immunomodulatory, anti-toxin, antioxidant, and many others. Honey has the potential to alleviate many lifestyle disorders, mitigate the adverse effects of drugs and toxins, and also provide healthy nutrition. Although conclusive clinical evidence is not available, yet honey may potentially be a safer alternative to sucrose for diabetic patients.

Poppy Intoxication in Infants and Children: Hazards of a Folk Remedy.

OBJECTIVE: To study the clinical and laboratory profile in infants and children presented in the tertiary care hospital with poppy intake and to compare the profile between those who survived with those who died. STUDY DESIGN:   Observational study. Study Place and Duration: Department Of Paediatrics, Mardan Medical Complex, Mardan, KPK, Pakistan from January 2019 to January 2020. METHODOLOGY: All the infants and children who reported during research period with signs and symptoms (one or more) of opium poppy intoxication, i.e. meiosis, respiratory depression and decreased consciousness level along with confirmed history of giving poppy at home. RESULTS: A total of 32 cases of opium poppy intoxication were admitted. Their age ranged from one month to 23 months, mean age was 7.22 + 5.43 months. Out of them, 15 (46.87%) infants and children survived, and 17 (53.13%) died, (p<0.001). The children who survived had significantly shorter period of time between poppy over-dose and admission in hospital as compared to those who had died (6.0 + 2.56 hours versus 12.47 + 4.14 hours, p<0.001). There was significantly high mortality in children who were given poppy powder mixed in water, out of 17 cases 13 died and 4 survived. Low respiratory rate, decreased oxygen saturation, aspiration pneumonia, apneic spells, cyanosis and leukocytosis >15000cc had significant effect on mortality. CONCLUSION: Poppy opium is very dangerous and hazardous for infants as it depresses respiration, causes coma; and can be fatal. People need to be educated to curb this harmful practice and authorities need to take necessary actions to stop the sale of poppy at shops and stores. Key Words: Poppy, poisoning/Intoxication, Infants, Meiosis, Apneic spell.

An Insight into Unani Hypoglycemic Drugs and Their Mechanism of Action.

BACKGROUND: Diabetes mellitus type-II is a major health problem characterized by hypoinsulinemia and insulin resistance, leading to hyperglycemia and its complications. In Unani medicine, it is known as ziyabetus. Several drugs are prescribed in Unani medicine as single and compound formulations for this disease. Most of these drugs have been studied on scientific parameters and shown significant activity in reducing the symptoms and complications of diabetes. OBJECTIVES: Critical evaluation of Unani medicines for treating diabetes patients have been conducted. The aim of the study is to provide complete information on this subject with the action of the mechanism so that proper treatment should be done with prospective research. METHODS: Unani literature was reviewed extensively via various search engines for the herbs, shrubs used for diabetes treatment. Ten drugs were selected for the present review. RESULTS AND CONCLUSION: There is convincing evidence to suggest that the selected drugs have promising actions against diabetes and its complications. In addition, none of the studies has reported any adverse effects with the drugs. Also, there is evidence to suggest that the method of usage described in Unani medicine may reduce or eliminate adverse events, if any. Further, there is a great need to do more research on making medicine more effective. Besides, the review article is useful for treating patients effectively by advancing the research.

Exploring new horizons in health care: A mechanistic review on the potential of Unani medicines in combating epidemics of infectious diseases.

The 20th and 21st centuries have witnessed epidemics and pandemics of various infectious agents. The development of effective antimicrobials in the 20th century has been complemented with the emergence of resistant and mutant strains. In this context, we present a comprehensive overview of the preventive measures described in Unani medicine during epidemics. Unani medicine is a traditional medicine system included in the Indian Systems of Medicine. Unani medicine has an extensive description of epidemic infections and preventive and therapeutic measures for the same. Certain factors like environment, season, and geographical location of a place are known to determine the extent of infections, and their escalation to epidemics. Maintenance of general health, immune-stimulation, and disinfecting of the environment are advised as protective measures, for which many drugs are prescribed. In the case of illness, specific antimicrobial drugs of natural origin are prescribed. Herein we discuss these measures in detail, along with the scientific evidences of anti-microbial, immunomodulatory, and health-protective actions of these drugs.

Topical medicines for wound healing: A systematic review of Unani literature with recent advances.

ETHNOPHARMACOLOGICAL RELEVANCE: Wound healing is an important area of research in contemporary medicine. Unani is a traditional medicine system based on hundreds of years of observations and experiences. Wounds are described under the headings qarha (arabic) and jarahat (persian) in classical Unani texts. Several drugs of herbal, mineral and animal origin are described in Unani texts as having wound healing properties. Many of these drugs have been screened on various scientific parameters but the potential of most drugs remains unexplored. METHODOLOGY: The study was aimed at summarizing the topical wound healing drugs mentioned in classical Unani books. The topical wound healing drugs were first identified in classical texts. Then 20 drugs were selected for detailed review on the basis of clinical relevance and wide availability. OBSERVATIONS AND RESULTS: Seventy drugs were identified in Unani texts after removal of duplicacy. Most of the drugs (85.71%) were of herbal origin, while 10% were of mineral origin and the rest 4.28% were of animal origin. Most of the herbal drugs belonged to the Fabaceae (10%) and Rosaceae (8.33%) families. Biologically active compounds such as phenols, sterols, hydrocarbons, anthocyanidins, flavonoids and tannins have been identified in almost all drugs which support classical literature. CONCLUSION: Unani system of medicine has a rich legacy of effective wound healing drugs, which is reinforced by modern researches. Most drugs exert their action on multiple phases of wound healing. In addition, most drugs have no reported adverse effects in laboratory and clinical studies. Hence, Unani medicine may offer the much-needed affordable and effective wound care in a wide range of clinical settings.

Overview of Covid-19; its prevention and management in the light of Unani medicine.

Since December 2019, a respiratory pandemic named as coronavirus disease 2019 (Covid-19) caused by a new coronavirus named as SARS-CoV-2, has taken the world by storm. The symptoms are fever, malaise, and cough which resolve in a few days in most cases; but may progress to respiratory distress and organ failure. Transmission is through droplet infection or fomites, but other modes such as airborne transmission and oro-fecal transmission are also speculated. Research is underway to develop effective vaccines and medicines for the disease. In such a scenario, we present the measures described in Unani system of medicine for health protection during epidemics. Unani is a traditional system of medicine developed during the middle ages, which employs natural drugs of herbal, animal and mineral origin for treatment. In Unani medicine, during an epidemic, apart from isolation and quarantine, three measures are of utmost importance, (i) purification of surroundings using certain herbal drugs as fumigants or sprays, (ii) health promotion and immune-modulation, and (iii) use of health-protecting drugs and symptom-specific drugs. Drugs such as loban (Styrax benzoides W. G. Craib), sandroos (Hymenaea verrucosa Gaertn.) za'fran (Crocus sativus L.), vinegar etc. are prescribed in various forms. Scientific researches on these drugs reveal the presence of a number of pharmacologically active substances, which may provide a new insight into the management of infections and epidemics.

Riluzole-loaded nanoparticles to alleviate the symptoms of neurological disorders by attenuating oxidative stress.

Purpose: The objective of the research undertaken was to develop the Riluzole (RIZ) nanoparticles drug delivery system using Transferrin (Tf) as a ligand in the brain.Method: RIZ-loaded chitosan nanoparticles and RIZ-Tf chitosan (CS) nanoparticles (RIZ CSNPs and RIZ-Tf CSNPs) were formulated and compared for particles size, size distribution, encapsulation efficiency, and surface morphology, respectively. The in vitro drug release, permeation, pharmacokinetic, biochemical, and pharmacodynamic experiments were done to assess the improvement in in vivo fate and efficacy of RIZ.Results: The size of optimized RIZ CSNPs was found to be 173.6 ± 2.23 nm and polydispersity index (PDI) of 0.264 ± 0.002 while that of RIZ-Tf CSNPs was 207 ± 2.49 nm and 0.406 ± 0.002. In vitro release was found to be 86.15 ± 7.316% and 91.1 ± 5.836%, respectively, while permeability coefficient was found to be 4 × 10-2 and 4.2 × 10-2 cm/s for RIZ CSNPs and RIZ-Tf CSNPs. The biochemical analysis studies revealed that oxidative stress was significantly decreased in case of RIZ CSNPs and RIZ-Tf CSNPs (p < 0.01) treated groups. The antianxiety effect and the memory restoration were evident in pharmacodynamic studies (p < 0.05) of the prepared formulations.Conclusion: The results of pharmacokinetic studies demonstrated the remarkable brain delivery of RIZ-Tf CSNPs through intranasal route as compared to the RIZ solution.

3D Printing Technology in Design of Pharmaceutical Products.

BACKGROUND: Three-dimensional printing (3DP) is a novel technology for fabrication of personalized medicine. As of late, FDA affirmed 3D printed tranquilize item in August 2015, which is characteristic of another section of Pharmaceutical assembling. 3DP incorporates a wide range of assembling procedures, which are altogether founded on computer-aided design (CAD), and controlled deposition of materials (layer-by-layer) to make freestyle geometries. Conventionally, many pharmaceutical processes like compressed tablet have been used from many years for the development of tablet with established regulatory pathways. But this simple process is outdated in terms of process competence and manufacturing flexibility (design space). 3DP is a new technology for the creation of plan, proving to be superior for complex products, customized items and items made on-request. It creates new opportunities for improving efficacy, safety, and convenience of medicines. METHOD: There are many of the 3D printing technology used for the development of personalized medicine on demand for better treatment like 3D powder direct printing technology, fused-filament 3D printing, 3D extrusion printer, piezoelectric inkjet printer, fused deposition 3D printing, 3D printer, ink-jet printer, micro-drop inkjet 3DP, thermal inkjet printer, multi-nozzle 3D printer, stereolithographic 3D printer. RESULT: This review highlights features how item and process comprehension can encourage the improvement of a control technique for various 3D printing strategies. CONCLUSION: It is concluded that the 3D printing technology is a novel potential for manufacturing of personalized dose medicines, due to better patient compliance which can be prepared when needed.

Role of P-Glycoprotein Inhibitors in the Bioavailability Enhancement of Solid Dispersion of Darunavir.

OBJECTIVE: The aim of the present study was to improve bioavailability of an important antiretroviral drug, Darunavir (DRV), which has low water solubility and poor intestinal absorption through solid dispersion (SD) approach incorporating polymer with P-glycoprotein inhibitory potential. METHODS: A statistical approach where design of experiment (DoE) was used to prepare SD of DRV with incorporation of P-glycoprotein inhibitors. Using DoE, different methods of preparation, like melt, solvent evaporation, and spray drying method, utilizing carriers like Kolliphor TPGS and Soluplus were evaluated. The optimized SD was characterized by DSC, FTIR, XRD, and SEM and further evaluated for enhancement in absorption using everted gut sac model, effect of food on absorption of DRV, and in vivo prospect. RESULTS AND DISCUSSION: DSC, FTIR, XRD, and SEM confirmed the amorphicity of drug in SD. Oral bioavailability studies revealed better absorption of DRV when given with food. Absorption studies and in vivo study findings demonstrated great potential of Kolliphor TPGS as P-glycoprotein inhibitor for increasing intestinal absorption and thus bioavailability of DRV. CONCLUSION: It is concluded that SD of DRV with the incorporation of Kolliphor TPGS was potential and promising approach in increasing bioavailability of DRV as well as minimizing its extrusion via P-glycoprotein efflux transporters.

Tacrolimus-loaded nanostructured lipid carriers for oral delivery-in vivo bioavailability enhancement.

The aim of the present study was to assess the Tacrolimus (TL) loaded nanostructured lipid carrier for enhancement in solubilisation potential, pharmacokinetic parameters and lymphatic distribution profile. The solubilisation potential of TL-NLC was determined via application of dynamic lipolysis models, which simulate the GIT environment and the intestinal conditions. The in vitro lipolysis studies revealed significantly high solubilisation (***p<0.001) of TL-NLCs in aqueous phase (69.3%) in contrast to TL suspension (1.6%) and the results were very well corroborated with in vivo AUC values of the corresponding formulations (R2>0.99). The in vivo, lymphatic and organ distribution studies were performed in albino wistar rats. There was marked increase of 7.2 folds in relative bioavailability of TL-NLC in comparison to TL suspension. Furthermore, study findings demonstrated that the lymphatic distribution of TL-NLC was enhanced by 19.25 folds in comparison to TL suspension. The results of dynamic lipolysis, bioavailability, lymphatic and other organ distribution studies confirmed that incorporation of TL in hybrid of lipids with different fatty acid chain length could substantially improve its in vivo prospect.

Tacrolimus-loaded nanostructured lipid carriers for oral delivery - Optimization of production and characterization.

Tacrolimus (TL), which is currently the mainstay of immunosuppressive therapy faces significant hurdles subsequent to its oral administration attributable to its poor aqueous solubility and extensive intestinal and hepatic first pass metabolism. Therefore, the present study aimed to design the stable nanostructured lipid carrier (NLC) of TL that would be able to overcome such hurdles. Capmul MCMC8 and Compritol 888ATO in 3:2 were selected as binary lipid phase on the basis of solubility study. An exhaustive screening of surfactants is done by aqueous titration to select the surfactant with best emulsifying potential and to optimize the concentration of lipids and surfactants in NLC. Different methods of preparation were explored and compared to optimize NLC which could have the best characteristic properties. TL-NLC was characterized for particle size, drug entrapment efficiency, crystal state, surface morphology and drug release. The obtained particle size, PDI and % drug entrapment efficiency of optimized formulations i.e., NLC-C2 and NLC-N2 were 70±5.42nm, 98±7.52nm; 0.43±0.081, 0.2±0.029 and 87±2.34%, 94±3.18%, respectively. The results of in vitro release studies showed significantly increased (***p<0.001) and sustained release of TL from NLC dispersions as compared to drug suspension (95.73% from NLC-C2, 99.86% from NLC-N2 and 9.27% drug suspension in pH 1.2 in 24h; 93.11% from NLC-C2, 96.65% from NLC-N2 and 10.2% drug suspension in pH 6.8 in 24h). The study demonstrated that proper selection of excipients (by aqueous titration) and modification of method of preparation (by inclusion of cold step) would lead to production of NLC with best characteristic properties.

Development and evaluation of solid dispersion of spironolactone using fusion method.

INTRODUCTION: Solubility and dissolution of a poor water-soluble drug are the two major barriers for formulation scientists in development of drug delivery. Many of the potent drugs do not show the therapeutic effects due to solubility issues but may show toxicity issues when used in high doses. Solid dispersion (SD) technology is an excellent tool for enhancing the solubility and dissolution and hence related bioavailability. MATERIALS AND METHODS: SD of spironolactone (SPL) was developed using an inert carrier polyethylene glycol 4000 (PEG 4000) by the conventional fusion method and characterized for various characterization parameters. RESULTS: Solubility of pure drug and SD of SPL in water was found to be 23.54 ± 1.75 µg/mL and 61.73 ± 1.26 µg/mL, respectively. The maximum cumulative percentage release from pure drug, SPL marketed product (tablet), physical mixture, and SPL SD at 60 min was 27.25 ± 1.83%, 35.64 ± 3.65%, 47.72 ± 2.45%, and 74.24 ± 3.25%, respectively in 0.1 N HCl. CONCLUSIONS: SD of SPL was developed successfully. The solubility of SPL SD was found to be significantly increased (P < 0.05) as compared to SPL active pharmaceutical ingredient (API) and physical mixture of PEG 4000 and SPL. The current study indicated that SD of SPL was a better option for enhancing solubility of a poorly soluble therapeutic agent.

Atorvastatin solid dispersion for bioavailability enhancement.

Atorvastatin calcium is a lipid-lowering agent. It has approximately 15% of bioavailability, remaining amount of drug showed adverse effect which is undesirable for patients. The objective of the study was to enhance the solubility and a dissolution profile of the atorvastatin (AT) calcium. Solid dispersion (SD) is a technique which enhances the solubility and a dissolution profile of poorly soluble drug. Various methods are being used for SDs such as microwave irradiation fusion, kneading, solvent evaporation, fusion, and dropping method. The authors have used here conventional fusion method using PEG 4000 as a hydrophilic carrier. The solubility of pure drug, physical mixture using PEG 4000 (1:3), and SD in phosphate buffer solutions (pH 6.8) was found to be 55.33 ± 0.66, 81.89 ± 2.35, and 93.66 ± 1.35, respectively. Fourier transform infrared and differential scanning calorimetry study showed the significant peak shift of drug in SD. It indicated that the nature of drug had been changed from crystalline form to amorphous form due to conversion into SD formulation. The dissolution rate was significantly increased when the drug polyethylene glycol 4000 ratio was 1:3. The mean cumulative percentage drugs release from pure drug, physical mixture, marketed tablet, and SD at 1 h was 28.92 ± 1.66%, 55.26 ± 0.95%, 72.16 ± 1.33%, and 91.66 ± 1.65%, respectively. It was concluded that the solubility and dissolution profile of SD of AT calcium showed the enhancement of solubility and dissolution when compared with marketed preparations.