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Bhardwaj Atul : Therapeutic effects of various morphological forms of Nasya in Pratishyaya

JPSI 1 (5), Sept – Oct 2012, 58-64

Journal of Pharmaceutical and Scientific Innovation www.jpsionline.com

Research Article

COMPARATIVE THERAPEUTIC EFFECTS OF VARIOUS MORPHOLOGICAL FORMS OF NASYA (NASAL ROUTE OF DRUG DELIVERY) IN PRATISHYAYA (RHINOSINUSITIS) WITH REFERENCE TO NASAL MUCO-CILIARY FUNCTION Bhardwaj Atul* Assistant Professor, Department of Shalakya Tantra, M.S.M. Institute of Ayurveda, B.P.S. Mahila Vishwavidyalaya, Khanpur Kalan, Sonipat-131305, Haryana, India. *Email: [email protected] Received on: 15/08/12 Revised on: 23/09/12 Accepted on: 05/10/12 ABSTRACT Different morphological forms of Nasyas (Nasal route of drug administration in Ayurveda) like Taila and Ghrita (lipid based nasal drops), churna (dry fine powder) and Avpeeda nasya (Aqueous based medicated decoction nasal drops) are commonly used as nasal drugs for the management of rhinological disorders in Ayurveda and they distinctly behave differently in the nasal cavity when introduced. This present study explores how these different morphological forms of Nasyas effects the nasal health and mucociliary mechanism in the patients of Pratishyaya i.e. Rhinosinusitis with the help of Goldman’s saccharin test which is carried out at various stages of this study. Clinically, endoscopically and radiologically diagnosed patients of Pratishyaya i.e. rhinosinusitis, satisfying the inclusion criteria were divided randomly by table method into four groups. A total of 40 patients were subjected in this trial after ramification into four trial groups with 10 patients in each group. Anu taila nasya, Shadbindu ghrita nasya, Katphala churna nasya and Pippali Avapeeda nasya respectively were selected for the present study in trial groups I – IV as they are the most frequently prescribed drugs in Ayurveda (Indian system of medicine) for the management of the disease Pratishyaya i.e. Rhinosinusitis. These selected drugs subtly represent medicated oils/lipids, powder insufflations (errhines) and medicated aqueous base decoction form of nasal drug administration when visualized in morphological appearance and modern perspective. Goldman’s saccharin test, which is used for the present study is a gold standard test for the evaluation of nasal mucociliary function and is directly related to nasal health. Powder form of nasal administered drug i.e. Katphala Churna nasya (powder form) was found to be most effective in improvement of endoscopic and radiological parameters of rhinosinusitis. Mucoadhesive properties of Anu Taila nasya and Shadbindu ghrita nasya (both lipid base Nasya) probably increases the physical weight on the mucosa thus deceases the ciliary transport transiently. Pippalyadi Avpeeda nasya (aqueous base nasal drops) was found to be most effective in enhancing mucociliary clearance activity. Key words: Ayurveda (Indian system of medicine), Nasya (Nasal route of drug administration in Ayurveda), Pratishyaya (Rhinosinusitis), Saccharin test, Mucociliary clearance mechanism (MCCM). INTRODUCTION While going through the Ayurvedic literature a vivid description of the disease ‘Pratishyaya’ is observed. There is descriptive mention of this disease with regard to aetiopathogenesis, classification, symptomatology, complications and management as ancient Ayurveda science was well versed with the concept of Pratishyaya. The disease is the most elaborated disorder among all ‘Nasa Rogas’ (rhinological disorders) but the description seems to be scattered at various places. The disease has got localized as well as somatic effects and accepted as a potential cause of ‘Kshya roga’ (emaciation) 1 and thus, the management of Pratishyaya should never be neglected or delayed in this respect. Different types type of Pratishyaya when gets complicated with added difficulties in treatment then a common term ‘Dusta Pratishyaya’ (complicated rhinosinusitis) is used.2 After evaluating the aetiological factors, symptomatology and complications of the disease Pratishyaya it seems quite prudent to accept that these features has got close proximity and compatibility with most common rhinological disorder termed as ‘Rhinosinusitis’. Rhinosinusitis affects millions of the population throughout the globe. Despite the enormity of the problem the pathophysiology of the disease still eludes the scientific community. Unfortunately the nose, with its convoluted architecture, is prone to obstructive diseases. Although the mucociliary pathways work harmoniously in health, infection can rapidly throw this delicate mechanism into disarray. 3 Most infection of the paranasal sinuses arise from primary focus in the nose and ciliary dysfunction being the most important factor responsible for the genesis of rhinosinusitis.

Anderson in 1974 introduces the use of Saccharin in estimating time interval between putting this saccharin in the nasal mucosa and perception of sweet taste as a diagnostic tool for the measurement of nasal mucociliary function. This ‘Saccharin test’ then becomes a gold standard diagnostic tool for the evaluation of ciliary function worldwide. 4 Three factors, however appears crucial for the normal physiological functioning of the nose and paranasal sinuses: normal mucociliary transport, patency of osteomeatal unit and normal quality and quantity of secretions. Disruption of any one or more factors can predispose rhinosinusitis. Mucociliary clearance mechanism (MCCM) is the most important of all of these factors and is the most important guiding factor in genesis of rhinosinusitis and is conformed by various histocytological, beat frequency, viscolastic, electron microscopic and ciliary dynamic studies of the nasal mucosa which is pseudostratified ciliary columnar in appearance histologically. The effect of various morphological forms of nasya (nasal route of drug administration) on this mucociliary mechanism does offer new horizons to explore the mode of action of action of different nasyas in combating the disease Pratishyaya i.e. rhinosinusitis. Different morphological forms of Nasyas used in Ayurveda like oil/lipid based nasal drops, dry fine powder (churna) and water based nasal drops (Avpeeda nasya/decoctions/infusions etc.) behaves differently in the nasal cavity when introduced. This present study intends to explore how these different morphological forms of nasyas affect the nasal health and mucociliary mechanism in the patients of Pratishyaya i.e. Rhinosinusitis with the help of Goldman’s saccharin test


JPSI 1 (5), Sept – Oct 2012, 58-64

which is carried out at various stages of this study. Anu taila nasya, Shadbindu ghrita nasya, Katphala churna nasya and Pippalyadi Avapeeda nasya are selected for the study as they are frequently prescribed in the management of Pratishyaya i.e. rhinosinusitis in Ayurvedic system of medicine and conspicuously represent medicated oils, medicated clarified butter, powder insufflations (errhines) and medicated aqueous base form of nasal drugs respectively when visualized in morphological appearance. The formulations scrutinized for the present study are mentioned in classical Ayurvedic texts and the fundamentals of Ayurvedic treatment were deemed respected in every sense in this endeavour but no work has been found in Ayurvedic literature regarding affect of various morphological forms of Nasya on mucociliary clearance mechanism. MATERIALS AND METHODS The present work is randomised, single blind, prospective and single centre study comprising patients of either sex in the age group 16-70 years. The patients for the research were selected from ENT OPD, M.S.M. Institute of Ayurveda, B.P.S. Mahila Vishwavidyalaya, khanpur kalan, Haryana. Established and diagnosed patients satisfying inclusion/exclusion and criteria of assessment were divided into four trial groups after having written and informed consent from the patient to participate in the study on a recorded and standardized proforma. The patient was also briefed about the research protocol, duration of trial, route of administration of drug prior to the consent. An official permission from institution’s research ethical committee and hospital core committee was also taken before the commencement of the trial (MSM/EC/SKT/2011/16). Statistical analysis The data was analysed for statistical significance by using statistical package for social sciences (SPSS Inc. Chicago, USA, 17.0). The student’s‘t’ test( paired) and one way analysis of variance (ANOVA) were used to analyze the data for the level of significance using ‘f’ ratio. The related‘t’ test was used to analyze intra group and ANOVA was used to find inter group differences in pre/post protocol. For all analysis the ‘p’ value used for statistical significance was 0.05 and the ANOVA used for the analysis was one way ANOVA. Selection of the patients: Inclusion criterion: · Clinically, endoscopically and radiologically diagnosed

patients of Pratishyaya i.e. rhinosinusitis. · Patients of age group 16-70 years. · Patients having various clinical features depicted in

criteria of assessment later. Exclusion criterion: · Patients exhibiting gross anatomical distortion of septum

or ostiomeatal complex impeding diagnostic Endoscopy. · Patients presenting with various complications of sinusitis

viz. intra orbital or intra cranial complications. · Patient having concomitant benign or malignant growth

of nasal cavity with rhinosinusitis. · Patients hypersensitive to local anaesthetic agent i.e.

lignocaine. Criteria of assessment for the present study Clinical features (Rhinological) a) Nasal obstruction/blockage b) Unilateral/bilateral discoloured nasal discharge

c) Decreased sense of smell d) Itching/irritation of nasal cavity Clinical features (Non rhinological) a) Headache b) Post nasal drip c) Itching/irritation of the throat d) Fullness/pressure of the ears Grading and scoring system of criteria of assessment: Visual analogue scale (VAS) was used for the grading and scoring of clinical features in the present study [Table 1]. Investigational parameters 1) Endoscopic parameters a) Polypoidal changes in the middle meatus b) Discharge in the middle meatus c) Oedema of the middle meatus d) Crusting of the middle meatus Done by using autoclavable 0o, 4mm rigid nasal endoscope with videoscopy unit. Grading and scoring of endoscopic parameters: For the present study Lund-Kennedy scale was adopted with practical modifications which has been recommended and endorsed by various sinonasal studies and also forwarded by IOS (international otolaryngology society), USA [Table 2]. This classification represents unilateral disease involvement and hence for bilateral representation this score should be doubled. Maximum score possible in case of unilateral presence of a disease is 4x2 =8, and in case of bilateral presence the maximum score available was 8x2 =16. 2) Radiological parameter Haziness of the different sinuses. X-ray PNS (OM’s view) with sitting position and open mouth and/or Coronal CT scan of PNS with 120 KV and 150 mA with 5mm interval and 2 sec. scan time. The slice thickness was 3mm for osteomeatal unit and 5mm for other sites. The window width was 2000 for the study. Grading and scoring of radiological parameters: For the present study Lund-Mackay scale was adopted with practical modifications which has been recommended and endorsed by various sinonasal studies and also forwarded by IOS, USA [Table 3]. This classification represents unilateral disease involvement and hence for bilateral representation this score should be doubled. Maximum score possible in case of unilateral presence of a disease is 4x2 =8, and in case of bilateral presence the maximum score available was 8x2 =16. 3) Saccharin mucociliary clearance test Time interval from instillation of saccharin in nasal valve area to perception of sweet taste by the patient was nominated as nasal mucociliary clearance time. This test of nasal mucociliary function was done as per recommendation of Anderson’s classical ‘Saccharin test’. Grading and scoring of nasal mucociliary clearance time Reproducibility of this test was also established by performing in 8 patients 2 weeks later after evaluating their initial MCCT. The reproducibility shows insignificant change from the initially recorded time value [Table 4]. Study design Diagnosed patients of Pratishyaya i.e. rhinosinusitis satisfying the inclusion criteria were randomly by table method, and divided into following four groups. A total of 46 patients were enrolled in the present trial of which 6 patients were dropout/lost in follow up [Table 5].


JPSI 1 (5), Sept – Oct 2012, 58-64

Overall results interpretation Overall results were adjudged in terms of percentage relief observed by the patients in pre described criteria of assessment (rhinological, non rhinological, endoscopic and

radiological parameters). This protocol of outcome of treatment is in accordance to global rating of response to treatment protocol [Table 6].

Table 1. Grading and scoring system of criteria of assessment

Clinical feature

0

1

2

3

4

5

Nasal obstruction/blockage No obstruction Mild obstruction

Moderate /bothersome obstruction

Moderately Severe

severe Very Severe

Discoloured nasal discharge No nasal Discharge

Mild nasal discharge

Moderate /bothersome

Moderately Severe

severe Very Severe

Decreased sense of smell/hyposmia

No hyposmia

Mild hyposmia


Moderately Severe

severe Very Severe

Itching/irritation of the nasal cavity

No itching/ Irritation

Mild Itching/ Irritation


Moderately Severe

severe Very Severe

Headache

No headache Mild Headache


Moderately Severe

severe Very Severe

Post nasal drip

No post nasal drip

Mild post Nasal drip


Moderately Severe

severe Very Severe

Itching/irritation of the throat

No itching/ Irritation

Mild Itching/ irritation


Moderately Severe

severe Very Severe

fullness/pressure of the ears No fullness/ Irritation

Mild Fullness/ irritation


Moderately Severe

severe Very Severe

Table 2. Lund-Kennedy scale (modified) for sinonasal studies

Criteria of assessment/ endoscopic observation

Score 0

Score 1

Score 2

Polyps in the middle meatus Absent Restricted to middle meatus Beyond the middle meatus Discharge in the middle meatus Absent Thin and clear discharge Thick and purulent Oedema of the middle meatus Absent Mild-moderate Moderate-severe Crusting in the middle meatus Absent Mild-moderate Moderate-severe

Table 3. Lund-Mackay scale (modified) for radiological parameters

Criteria of assessment/radiological observations Score 0 Score 1 Score 2 Maxillary sinus No haziness Mild haziness Complete haziness

Frontal sinus No haziness Mild haziness Complete haziness Ethmoidal sinus No haziness Mild haziness Complete haziness Sphenoid sinus No haziness Mild haziness Complete haziness

Table 4. Nasal mucociliary clearance time:

Mucociliary clearance time (MCCT)

Grading Scoring

<,=30 minutes Normal 0 >,=31-<,=40 minutes Mildly increased 1 >,=41-<,=50 minutes Moderately increased 2

>,= 50 Severely increased 3

Table 5. Study design and preamble of drug protocol Trial group Morphological form

of Nasya No. of patients (dissociated)

Dosage Duration of trial

Follow up

I

Anu taila nasya (lipid)

10

6 drops in each nostril

21 days

For 2 months

II

Shadbindu ghrita nasya (lipid)

10


21 days

For 2 months

III

Katphala churna nasya (powder)

10

1 Shana(total dose of 4 gms twice daily)

21 days

For 2 months

IV

Pippalyadi avpeeda nasya (Aqueous

base)

10


21 days

For 2 months


JPSI 1 (5), Sept – Oct 2012, 58-64

Table 6. Overall results

Treatment outcome Percentage relief Cured 100% relief

Markedly improved >75% relief Moderately improved >,= 50% - <,= 75% relief

Slightly improved >,= 25% - < 50% relief Unchanged/ unimproved < 25% relief Deteriorated/worsened Negative % relief

Table 7. Effect of Anu taila nasya in 10 patients of rhinosinusitis in group I

Signs and symptoms n Mean X(d) B.T.-A.T.

% relief

S.D.+/- S.E.+/- ‘t’ value

‘p’ value B.T. A.T.

Nasal obstruction 10 2.6 1.2 1.4 53.84 0.699 0.221 6.33 P<0.001 Discoloured nasal discharge 10 1.9 0.7 1.2 63.15 0.632 0.2 6 P<0.001

Decreased sense of smell/hyposmia 9 2.7 1.4 1.3 48.14 0.675 0.213 6.09 P<0.001 Itching/irritation of the nasal cavity 10 1.9 0.7 1.2 63.15 0.632 0.2 6 P<0.001

Headache 7 2.6 1.3 1.3 50 0.675 0.213 6.09 P<0.001 Post nasal drip 8 2.3 1.2 1.1 47.82 0.316 0.1 11 P<0.001

Itching/irritation of the throat 8 1.8 0.8 1 55.55 0.471 0.149 6.71 P<0.001 fullness/pressure of the ears 7 2.3 1.3 1 43.47 0.667 0.211 4.74 P<0.05

Endoscopy 10 8.1 4.9 3.2 39.5 2.098 0.663 4.82 P<0.001 Radiology 10 7.1 4.6 2.5 35.21 1.080 0.342 7.32 P<0.001

Mucociliary clearance time 10 1.6 0.8 0.8 44.44 0.422 0.133 6 P<0.001

Table 8. Effect of Shadbindu ghrita nasya in 10 patients of rhinosinusitis in group II Signs and symptoms n Mean X(d)

B.T.-A.T.

% relief



Nasal obstruction 10 2.7 0.9 1.8 66.66 0.789 0.249 7.22 P<0.001 Discoloured nasal discharge 9 2.1 0.8 1.3 61.90 0.823 0.260 4.99 P<0.001

Decreased sense of smell/hyposmia 9 2.2 0.7 1.5 68.18 0.707 0.224 6.71 P<0.001 Itching/irritation of the nasal cavity 9 3.1 2 1.1 35.48 0.316 0.1 11 P<0.001

Headache 7 2.3 1.1 1.2 52.17 0.422 0.133 9 P<0.001 Post nasal drip 8 2.6 1.2 1.4 53.84 0.699 0.221 6.33 P<0.001

Itching/irritation of the throat 8 3.1 1.7 1.4 45.16 0.699 0.221 6.33 P<0.001 fullness/pressure of the ears 7 2.9 1.7 1.2 41.37 0.789 0.249 4.81 P<0.001

Endoscopy 10 6.6 4.2 2.4 36.36 2.171 0.686 3.5 P<0.05 Radiology 10 5.8 3.9 1.9 32.75 0.316 1 19 P<0.001

Mucociliary clearance time 10 1.6 0.5 1.1 68.75 0.568 0.180 6.13 P<0.001

Table 9. Effect of Katphala churna nasya in 10 patients of rhinosinusitis in group III Signs and symptoms N Mean X(d)

B.T.-A.T.

% relief



Nasal obstruction 10 3.1 1.3 1.8 58.06 0.632 0.2 9 P<0.001 Discoloured nasal discharge 10 2.2 0.8 1.4 63.63 0.516 0.163 8.57 P<0.001

Decreased sense of smell/hyposmia 9 2.9 1.2 1.7 58.62 0.483 0.153 11.13 P<0.001 Itching/irritation of the nasal cavity 10 3.2 1.1 2.1 65.62 0.876 0.277 7.58 P<0.001

Headache 7 2.5 0.6 1.9 76 0.876 0.277 6.86 P<0.001 Post nasal drip 9 2.8 1.2 1.6 57.14 0.843 0.267 6 P<0.001


Endoscopy 10 6.8 3.5 3.3 48.52 2.003 0.633 5.21 P<0.001 Radiology 10 6.4 3.4 3 46.87 1.563 0.494 6.04 P<0.001


Table 10. Effect of Pippalyadi Avapeeda nasya in 10 patients of rhinosinusitis in group IV Signs and symptoms N Mean X(d)

B.T.-A.T.

% relief



Nasal obstruction 10 2.5 1 1.5 60 0.707 0.224 6.71 P<0.001 Discoloured nasal discharge 9 2.4 1 1.4 58.33 0.699 0.221 6.33 P<0.001

Decreased sense of smell/hyposmia 9 2 0.3 1.7 85 0.823 0.260 6.53 P<0.001 Itching/irritation of the nasal cavity 9 2.9 0.6 2.3 79.31 0.823 0.260 8.83 P<0.001

Headache 7 3 0.9 2.1 70 0.994 0.314 6.68 P<0.001 Post nasal drip 7 2.7 1.1 1.6 59.25 0.699 0.221 7.24 P<0.001


Endoscopy 10 7.7 4.2 3.5 45.45 1.841 0.582 6.01 P<0.001 Radiology 10 8.2 3.8 4.4 53.65 1.350 0.427 10.31 P<0.001



JPSI 1 (5), Sept – Oct 2012, 58-64

Table 11. One way ANOVA for comparing inter group efficacy of different morphological forms Criteria of assessment(Signs and

Symptoms) Sum of squares df(degree of freedom) mean sum of

square ‘f’

ratio Sig(p)

Between groups

Within group

Between groups

Within group

Between groups

Within group

Nasal obstruction 1 30.6 3 36 0.333 0.850 0.39 0.795 Discoloured nasal discharge 0.475 21.3 3 36 0.158 0.592 0.27 0.848

Decreased sense of smell/hyposmia 7.4 36.20 3 36 2.47 1.01 2.45 0.079 Itching/irritation of the nasal

cavity 12.20 37.40 3 36 4.07 1.04

3.91 0.016

Headache 2.68 42.30 3 36 0.89 1.17 0.76 0.525 Post nasal drip

0.08 47.70 3 36 0.03 1.33 0.02 0.996

Itching/irritation of the throat 4.20 42.20 3 36 1.40 1.17 1.19 0.326 fullness/pressure of the ears 2.70 59.20 3 36 0.90 1.64 0.55 0.653

Endoscopy 9.80 144.60 3 36 3.27 4.02 0.81 0.495 Radiology 7.48 189.30 3 36 2.49 5.26 0.47 0.702

Mucociliary clearance time 1.3 12.60 3 36 0.433 0.350 1.24 0.310

Table 12. Mean of various clinical parameters (after treatment value) in all four groups Signs and symptoms Anu taila nasya

(Group I) Shadbindu ghrita

(Group II) Katphala churna

(Group III) Pippalyadi avpeeda

(Group IV) Nasal obstruction 1.2 0.9 1.3 1

Discoloured nasal discharge 0.7 0.8 0.8 1 Hyposmia 1.4 0.7 1.2 0.3

Itching/irritation of the nasal cavity 0.7 2 1.1 0.6 Headache 1.3 1.1 0.6 0.9

Post nasal drip 1.2 1.2 1.2 1.1 Itching/irritation of the throat 0.8 1.7 1.2 1.1 fullness/pressure of the ears 1.3 1.7 1.7 1.1

Endoscopy 4.9 4.2 3.5 4.2 Radiology 4.6 3.9 3.4 3.8

Mucociliary clearance time 0.8 0.5 0.6 0.3

Table 13. Overall outcome of the treatment in all four trial Groups Outcome of the

treatment Group I

(Anu taila nasya) Group II

(Shadbindu Ghrita nasya) Group III

(Katphala Churna nasya) Group IV

(Pippalyadi Avpeeda nasya) Cured 0 0 0 0

Markedly improved 0 0 0 0 Moderately improved 2 3 8 9

Slightly improved 8 7 2 1 Unchanged 0 0 0 0 Deteriorated 0 0 0 0

Total 10 10 10 10 OBSERVATIONS AND RESULTS The treatment in this group consists of Anu tail nasya, Shadbindu ghrita nasya, Katphala churna nasya and Pippalyadi Avapeeda nasya by dividing 40 in four trial groups i.e. I, II, III, IV and having 10 patients and each group receiving different morphological form of nasya i.e. Taila (medicated Oil), Grita (medicated clarified butter), Churna (medicated Powder) and Avpeeda nasya (medicated juice/decoction) respectively. Paired‘t’ test is used for the evaluation of effectiveness [Table 7, 8, 9, 10] of individual groups. Inter group comparison of effectiveness of therapy in Group I, II, III, IV between different morphological forms of nasyas: The treatment in four different groups consists of Anu taila nasya, Shadbindu ghrita nasya, Katphala churna nasya and Pippalyadi Avapeeda nasya by dividing 40 patients of this group into 4 groups of 10 patients and each group receiving different morphological form of nasya i.e. taila, grita, churna and decoction respectively. After exploring the effectiveness of individual effect in all 4 groups by applying paired ‘t’ test, it is also important to explore which morphological form of Nasya has got more efficiency to combat various signs and symptoms (criteria of assessment) of Pratishyaya i.e. rhinosinusitis. As in accordance to research methodology

guidelines in these comparisons of more than two trial groups, analysis of variance (ANOVA) was all performed on all criterion of assessment [Table 11]. The critical ‘f’ value in case of all groups viz. group I-IV was 2.86. Although in all four groups, Anu taila nasya was found to be most effective in combating discoloured nasal discharge and itching/irritation of the throat, Shadbindu ghrita nasya was found to be most effective in combating nasal obstruction, Katphala churna nasya was found to be most effective in combating headache, endoscopic parameters, and radiological parameters, Pippalyadi avpeeda nasya was found to be most effective in combating hyposmia, Itching/irritation of the nasal cavity, post nasal drip, fullness of the ears and mucociliary clearance time reversal. In inter group comparison none of the four different morphological forms of nasyas was observed superior to other as the difference was found to be statistically insignificant in all clinical parameters (all calculated ‘f’ ratios are less than the critical valve) except itching/irritation of the nasal cavity in which Group II i.e. Shadbindu ghrita nasya was found to be most effective (f ratio = 3.91). This particular observation was done on the basis of comparing means of after treatment in different trial groups [Table 12].


JPSI 1 (5), Sept – Oct 2012, 58-64

DISCUSSION Mucociliary clearance (MCC) is a physiological function of the nasal cavity and respiratory tract to clear locally produced debris, excessive secretions or unwanted inhaled particles. For normal MCC to occur it is necessary that the epithelial cells are intact the ciliary activity and the rheology of mucus are normal and that the depth and chemical composition of the periciliary fluid layer is optimal. For many years drugs has been administered nasally for both topical and systemic action. Topical administration includes the treatment of congestion, rhinitis, sinusitis and related allergic or chronic conditions. Various morphological forms of drugs are used for nasal drug delivery in experimental studies or in market i.e. aqueous nasal drops, oil based nasal drops, nasal sprays, nasal gel pumps, pressurized metered dose inhalers (MDIs) and dry powder inhalers. 5 Intranasal delivery is currently being employed in treatments for migraine, smoking cessation, acute pain relief, osteoporosis, nocturnal enuresis and vitamin B12 deficiency 6 in modern system of medicine. Powder form of nasal drug administration and nasal health The transportability of mucus from patients with cystic fibrosis and bronchiectasis has recently been shown to increase markedly when incubated with dry powders of hyperosmotic agents such as sodium chloride, urea, mannitol and glucose. 7 The reason for this is not known but an alteration in the rheological properties of the mucus was suggested. Increasing the Osmolarity of the airway fluid by inhaling a dry-powder preparation increases mucociliary clearance in healthy subjects. The mechanism of this increase in clearance remains unclear but it is likely that hyperosmolarity stimulates ciliary beat frequency indirectly through intracellular biochemical changes. Dry powder may also alter the rheological properties of the mucus as it is reported to increase transportability of mucus. 8 The present study reiterates the up stated mechanism of enhancing ciliary beat frequency. Although Pippalyadi Avapeeda nasya was found to be most effective in enhancing mucociliary beat frequency which was evaluated by Goldman’s Saccharine test among all the groups, Katphala Churna nasya also increased ciliary beat frequency which is reflected by analyzing the overall results [Table 13]. This effectiveness of Katphala Churna nasya can be explained by the wide spreading property of a powder on inhalation and inherent trait of possibility of reaching the all important ‘osteomeatal complex’ which is the key area in genesis of rhinosinusitis and always needs to be addressed in each and every case of rhinological disorders. Modern rhinology firmly believes that reversal of ciliary beat frequency will surely reverse the rhinosinusitis as pathology. Katphala Churna nasya was also found to most effective in improvement in endoscopic and radiological parameters in intergroup comparison which is directly related to nasal mucociliary function. Oil/lipid base nasal drops and nasal health Oil/lipid base nasal drops are high viscosity thickened solutions or suspensions. The advantages of oily nasal drops includes reduction of post nasal drip due to high viscosity, reduction of taste impact due to reduced swallowing, reduction of anterior leakage of the formulation, reduction of irritation by using soothing/emollient excipients and target delivery to mucosa for better absorption. 9

The intranasal route may be a viable alternative for self-administration, whereby these limitations could be overcome. However, the problem associated with nasal delivery of aqueous nasal drops is lower retention time of solution in nasal cavity (15 minutes) resulting in lower bioavailability as well as lower transfer of drug directly to the brain through the olfactory pathway. 10 Hence, a formulation that would increase residence time in the nasal cavity and at the same time increase absorption of the drug would be highly beneficial in all respects. The use of lipid base nasal drops can lengthen the residence time and enhance bioavailability of drugs delivered to the nasal cavity. 11 Lipid formulations that provide in situ gelling property in nasal cavity were designed to delay clearance of the formulations to give optimum mucoadhesive strength. 12 Further increase in contact time did not affect the mucoadhesive strength, whereas decreased contact time resulted in less mucoadhesive strength resulting from insufficient time for entanglement of polymer chains with mucin in the nasal cavity. The microscopic observations indicate that the optimized formulation has no significant effect on the microscopic structure of mucosa. The epithelium layer was intact and there were no alterations in basal lamina with lipid treated nasal mucosa. Thus lipid formulations seem to be safe with respect to nasal administration. Lipid base nasal drops favourable rheological and mucoadhesive properties to allow the formulation to gel and adhere to the nasal mucosa after intranasal instillation, thereby decreasing clearance of the formulation at the site of instillation and enhancing drug absorption. Oil based nasal drops is a promising nasal drug delivery system for the sinonasal disorders, which would enhance nasal residence time owing to increased viscosity and mucoadhesive characteristics; furthermore, it also exhibited a permeation enhancing effect. This present study also supports the fact that mucoadhesive properties of Anu Taila nasya and Shadbindu ghrita nasya probably enhance the absorption of the drug by enhancing contact time with mucociliary belt but unfortunately at the same time they increases the physical weight on the mucosa thus deceases the ciliary transport transiently. In the active stage of inflammation of nasal mucosa i.e. rhinosinusitis when the nasal and sinuses are already overloaded with exudates/transudates because of capillary bed dilatation and active secretion from goblet cells it is not prudent enough to still overload the already diseased cilias with oil based nasal drops (both Taila and Ghrita are lipid based nasal drops in morphological point of view). This is the reason why Nasya karma (nasal route of drug administration) is condemned in active stage (Aama avastha) of the diseases in Ayurvedic classical texts which is well supported by modern researches also. In the present study also both lipid based nasal drops i.e. Anu Taila nasya and Shadbindu Ghrita nasya has got least effect on nasal mucociliary clearance time, but when inter group comparison are made although this difference is found to be statistically insignificant. In overall result comparison also Anu Taila nasya and Shadbindu Ghrita nasya are found to be least effective in intergroup comparison. Apart from this fact radiological and endoscopic parameters are also least effected by these two trial groups. Aqueous base nasal drops and nasal health Aqueous preparations are the most widely used dosage forms for nasal administration of drugs. They are mainly based on


JPSI 1 (5), Sept – Oct 2012, 58-64

aqueous state formulations. Their humidifying effect is convenient and useful, since many allergic and chronic diseases are often connected with crusts and drying of mucous membranes. Microbiological stability, irritation and allergic rhinitis are the major drawbacks associated with the water-based dosage forms because the required preservatives impair mucociliary function and the reduced chemical stability of the dissolved drug substance and the short residence time of the formulation in the nasal cavity are major disadvantages of liquid formulations. In the present study Pippalyadi Avpeeda nasya was found to be most effective in enhancing mucociliary clearance activity and resolving the signs and symptoms of Rhinosinusitis in Group IV. This observation is further supported by the fact that this group is found to be most effective in overall results. Incomplete absorption of some drugs following oral administration and first-pass metabolism, results in a low absolute bioavailability. Unfortunately, potential drugs for the treatment of most brain diseases are therefore often not able to cross these barriers. 11 As a result, various drug delivery and targeting Strategies are currently being developed to enhance the transport and distribution of drugs into the brain. Nasal drug delivery is an emerging technique and even better option to transport the drug directly to brain bypassing the metabolism. The Delivery from nose to central nervous system occurs within minutes along with both the olfactory and trigeminal neural pathways. 13 CONCLUSION Analysis of mucociliary clearance can provide grounds for suspected diagnosis of certain diseases of rhinology. Goldman’s saccharin test, which is used for the present study is a gold standard test for the evaluation of nasal mucociliary function and hence directly related to nasal health. Saccharine test is useful for scientific investigations of nasal mucociliary function, easy to perform, without the need of sophisticated equipment, and don’t cause much subject discomfort. Different morphological forms of nasyas like lipid based nasal drops, dry fine powder (Churna) and aqueous based nasal drops (Avpeeda nasya)) tends to affect the ciliary epithelium differently in the nasal cavity when administered. Inhaling a dry-powder preparation increases mucociliary clearance in patients of Pratishyaya and dry powder may also alter the rheological properties of the mucus and certainly increases transportability of mucus. In the present study Katphala Churna Pradhmana nasya was also found to most effective in improvement in endoscopic and radiological parameters in all the groups, which subtly is directly corresponds to improvement in ciliary function. In the present study also both lipid based nasal drops i.e. Anu Taila nasya

and Shadbindu Ghrita snehana nasya has got least effect on nasal mucociliary clearance in all the trial groups. This present study also supports the fact that mucoadhesive properties of Anu Taila Sneha nasya and Shadbindu ghrita Snehana nasya probably enhance the absorption of the drug by enhancing contact time with mucociliary belt but at the same time they increases the physical weight on the mucosa thus deceases the ciliary transport transiently. Aqueous base/decoctions form of nasal administration of drugs frequently requires preservatives which probably impair mucociliary function and the reduced chemical stability of the dissolved drug substance and the short effective contact time of these formulations in the nasal cavity are major disadvantages of aqueous formulations. The present effort is a pilot study and the inferences drawn needs to be strengthened by organizing a large sample study having different morphological forms of drugs administered through nasal cavity. REFERENCES 1. Agnivesha, Charaka, Dridhabala, Charaka Samhita, Nidana sthana,

Apasmara nidana Adhyaya, 8/18, edited by Pt. Rajeshwar Dutta, 2nd edition, 2003 reprint, Chaukhambha Bharti Academy, 2003:666.

2. Susruta, Kaviraj Ambikadutt Shastri, Sushruta Samhita, Uttar Tantra, Pratishyaya pratishedha Adhyaya, 24/16, 11th ed., Chaukhambha Sanskrit Sansthan,1998:119.

3. Ballenger JJ, Snow james B. Otorhinolaryngology: head and neck surgery. 15th ed. PA(USA): Williams & Wilkins; 1996:163.

4. Valia Pedro, Valero Franciso, Pardo Julio Marin, Rentro Daniel, Monte Carmen. Saccharin test for the study of mucociliary clearance: Reference values for a Spanish population. Arch Bronconeumol. 2008;44(10):540-5.

5. L Thorsson, O Borga, S Edsbacker. Systemic availability of budesonide after administration of three different formulations: pressurized aerosol, aqueous pump spray and powder. Br J Clinical Pharmacol. 1999 june;46(6):619-24.

6. Chand DR, Datta Maurya, Kumar Tilak vijay, Gupta Anish, Dangi Girija. A review on factors affecting the design of nasal drug delivery system. International research journal of pharmacy. 2010 dec;1(1):29-42.

7. Scott H. Doladson, Timothy E. Corcoran, Beth L. Laube, William D. Bennett. Mucociliary clearance as an outcome measure for cystic fibrosis clinical research. Proceedings of the American thoracic society.2007;4:399-405.

8. E. Daviskas, S.D. Anderson, J.D. Brannan, H. Chan, S. Eberl, G. Bautovich. European respiratory journal. 1997;10:2449-54.

9. T. Bjork, M Gunnarsson, M Holmstrom, A Nordqvist, B Petruson. Rhinology.2000;38:200-3.

10. David Shoseyov, Haim Bibi, Pintov Shai, Nurit Shosayou, Gila Shzberg, Haggit Hurvitz. Treatment with hypertonic saline versus normal saline nasal wash of paediatric chronic sinusitis. Mosby, Inc. 1997;91:6749.

11. M. Alagusundaram, B. Chengiah, K. Gnanaprakash, S. Ramkanth, C. Madhuaudhana Chetty, D. Dhachinamoorthi. Nasal drug delivery system - an overview. Int. J Res. Pharm. 2010;1(4):454-65.

12. Rita j. Majithiya, Pradip K. Ghosh, Manish L. Umrethia, Rayasa S. Murthy, Thermo reversible – mucoadhesive Gel for nasal delivery of Sumatriptan. AAPS PharmSci. 2006;7(3):Article 67.

13. J.S. Paun, A.A. Bagada, M.K. Raval. Nasal drug Delivery – As an effective tool for brain targeting – A review. International journal of Pharmaceutical and applied sciences. 2010;1(2):43-55.

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How to cite this article: Atul Bhardwaj, Comparative therapeutic effects of various morphological forms of Nasya (Nasal route of drug delivery) in Pratishyaya (Rhinosinusitis) with reference to Nasal Muco-ciliary function. J Pharm Sci Innov. 2012; 1(5): 58-64.

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